16-2326475-T-C

Variant names:

Variant summary

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

The ENST00000563623.5(ABCA3):n.555A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,608,992 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 23 hom. )

Consequence

ABCA3
ENST00000563623.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.11

Publications

3 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 (REVEL=0.01).

BP6

Variant 16-2326475-T-C is Benign according to our data. Variant chr16-2326475-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00973 (1482/152332) while in subpopulation AFR AF = 0.0337 (1402/41564). AF 95% confidence interval is 0.0323. There are 23 homozygotes in GnomAd4. There are 720 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA3	NM_001089.3 link	c.-9A>G		5_prime_UTR_variant	Exon 4 of 33	ENST00000301732.10	NP_001080.2	Q99758-1Q4LE27

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA3	ENST00000563623.5 link	n.555A>G	non_coding_transcript_exon_variant	Exon 4 of 20	1
ABCA3	ENST00000301732.10 link	c.-9A>G	5_prime_UTR_variant	Exon 4 of 33	1	NM_001089.3	ENSP00000301732.5	Q99758-1
ABCA3	ENST00000382381.7 link	c.-9A>G	5_prime_UTR_variant	Exon 4 of 32	1		ENSP00000371818.3	H0Y3H2
ABCA3	ENST00000567910.1 link	c.-9A>G	5_prime_UTR_variant	Exon 3 of 6	1		ENSP00000454397.1	Q99758-2

Frequencies

GnomAD3 genomes

AF:

0.00972

AC:

1479

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00248

AC:

594

AN:

239772

AF XY:

0.00177

show subpopulations

Gnomad AFR exome

AF:

0.0336

Gnomad AMR exome

AF:

0.00187

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.00106

AC:

1549

AN:

1456660

Hom.:

Cov.:

AF XY:

0.000870

AC XY:

630

AN XY:

724084

show subpopulations

African (AFR)

AF:

0.0334

AC:

1113

AN:

33360

American (AMR)

AF:

0.00220

AC:

AN:

44106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25964

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.000117

AC:

AN:

85348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52908

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000152

AC:

169

AN:

1109450

Other (OTH)

AF:

0.00236

AC:

142

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00973

AC:

1482

AN:

152332

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

720

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0337

AC:

1402

AN:

41564

American (AMR)

AF:

0.00301

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68032

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00500

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 04, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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

-9A>G in exon 4 of ABCA3: This variant is not expected to have clinical signific ance because it has been identified in 3.3% (146/4396) of African American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.67

(source)

DANN

Benign

0.43

PhyloP100

-1.1

Mutation Taster

=299/1

polymorphism

(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