rs117031141

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001089.3(ABCA3):c.447+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,587,038 control chromosomes in the GnomAD database, including 524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 48 hom., cov: 31)

Exomes 𝑓: 0.024 ( 476 hom. )

Consequence

ABCA3
NM_001089.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.19

Publications

2 publications found

Variant links:

Genes affected

ABCA3 (HGNC:33): (ATP binding cassette subfamily A member 3) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. The full transporter encoded by this gene may be involved in development of resistance to xenobiotics and engulfment during programmed cell death. [provided by RefSeq, Jul 2008]

ABCA3 Gene-Disease associations (from GenCC):

interstitial lung disease due to ABCA3 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ABCA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-2324393-G-A is Benign according to our data. Variant chr16-2324393-G-A is described in ClinVar as Benign. ClinVar VariationId is 162675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0194 (2961/152286) while in subpopulation NFE AF = 0.0275 (1871/68008). AF 95% confidence interval is 0.0265. There are 48 homozygotes in GnomAd4. There are 1428 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3 link	c.447+11C>T		intron_variant	Intron 6 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ABCA3	ENST00000301732.10 link	c.447+11C>T	intron_variant	Intron 6 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7 link	c.447+11C>T	intron_variant	Intron 6 of 31	1		ENSP00000371818.3
ABCA3	ENST00000567910.1 link	c.447+11C>T	intron_variant	Intron 5 of 5	1		ENSP00000454397.1
ABCA3	ENST00000563623.5 link	n.1010+11C>T	intron_variant	Intron 6 of 19	1

Frequencies

GnomAD3 genomes

AF:

0.0195

AC:

2965

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00463

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0161

Gnomad FIN

AF:

0.0410

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0275

Gnomad OTH

AF:

0.0163

GnomAD2 exomes

AF:

0.0179

AC:

3797

AN:

211748

AF XY:

0.0185

show subpopulations

Gnomad AFR exome

AF:

0.00408

Gnomad AMR exome

AF:

0.00792

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0249

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0238

AC:

34194

AN:

1434752

Hom.:

476

Cov.:

AF XY:

0.0236

AC XY:

16812

AN XY:

712548

show subpopulations

African (AFR)

AF:

0.00362

AC:

120

AN:

33140

American (AMR)

AF:

0.00829

AC:

346

AN:

41740

Ashkenazi Jewish (ASJ)

AF:

0.0269

AC:

689

AN:

25654

East Asian (EAS)

AF:

0.0000770

AC:

AN:

38986

South Asian (SAS)

AF:

0.0120

AC:

1004

AN:

83580

European-Finnish (FIN)

AF:

0.0312

AC:

1310

AN:

42000

Middle Eastern (MID)

AF:

0.0234

AC:

129

AN:

5508

European-Non Finnish (NFE)

AF:

0.0266

AC:

29334

AN:

1104482

Other (OTH)

AF:

0.0211

AC:

1259

AN:

59662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1933

3865

5798

7730

9663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1090

2180

3270

4360

5450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0194

AC:

2961

AN:

152286

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1428

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00462

AC:

192

AN:

41554

American (AMR)

AF:

0.0123

AC:

188

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0164

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0410

AC:

435

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0275

AC:

1871

AN:

68008

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

142

285

427

570

712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0245

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

447+11C>T in intron 6 of ABCA3: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 2.4% (210/8594) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS; dbSNP rs117031141). -

Interstitial lung disease due to ABCA3 deficiency

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Hereditary pulmonary alveolar proteinosis

Benign:1

Aug 23, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.18

(source)

DANN

Benign

0.56

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over