rs117031141

Positions:

Variant summary

Our verdict is Benign. Variant got -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:4

Conservation

PhyloP100: -1.19

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 162675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2324393-G-A is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA3	NM_001089.3 linkuse as main transcript	c.447+11C>T		intron_variant		ENST00000301732.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ABCA3	ENST00000301732.10 linkuse as main transcript	c.447+11C>T	intron_variant	1	NM_001089.3	P1	Q99758-1
ABCA3	ENST00000382381.7 linkuse as main transcript	c.447+11C>T	intron_variant	1
ABCA3	ENST00000567910.1 linkuse as main transcript	c.447+11C>T	intron_variant	1			Q99758-2
ABCA3	ENST00000563623.5 linkuse as main transcript	n.1010+11C>T	intron_variant, non_coding_transcript_variant	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

GnomAD3 exomes

AF:

0.0179

AC:

3797

AN:

211748

Hom.:

AF XY:

0.0185

AC XY:

2133

AN XY:

115476

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 SAS exome

AF:

0.0113

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

Gnomad4 AFR exome

AF:

0.00362

Gnomad4 AMR exome

AF:

0.00829

Gnomad4 ASJ exome

AF:

0.0269

Gnomad4 EAS exome

AF:

0.0000770

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.0312

Gnomad4 NFE exome

AF:

0.0266

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

AF:

0.0194

AC:

2961

AN:

152286

Hom.:

Cov.:

AF XY:

0.0192

AC XY:

1428

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00462

Gnomad4 AMR

AF:

0.0123

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.0410

Gnomad4 NFE

AF:

0.0275

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0252

Hom.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Feb 21, 2013

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Hereditary pulmonary alveolar proteinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2018

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

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over