rs13332547

chr16-2317423-G-Achr16-2317423-G-Cchr16-2317423-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001089.3(ABCA3):c.991-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,612,662 control chromosomes in the GnomAD database, including 16,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1712 hom., cov: 31)

Exomes 𝑓: 0.12 ( 14954 hom. )

Consequence

ABCA3
NM_001089.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.113

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-2317423-G-A is Benign according to our data. Variant chr16-2317423-G-A is described in ClinVar as [Benign]. Clinvar id is 1249107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA3	NM_001089.3 linkuse as main transcript	c.991-20C>T		intron_variant		ENST00000301732.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ABCA3	ENST00000301732.10 linkuse as main transcript	c.991-20C>T	intron_variant	1	NM_001089.3	P1	Q99758-1
ABCA3	ENST00000382381.7 linkuse as main transcript	c.991-20C>T	intron_variant	1
ABCA3	ENST00000563623.5 linkuse as main transcript	n.1554-20C>T	intron_variant, non_coding_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19345

AN:

151948

Hom.:

1699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.0926

Gnomad OTH

AF:

0.138

GnomAD3 exomes

AF:

0.172

AC:

43008

AN:

249976

Hom.:

5790

AF XY:

0.162

AC XY:

21960

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.410

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.378

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.0946

Gnomad NFE exome

AF:

0.0958

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.121

AC:

177303

AN:

1460596

Hom.:

14954

Cov.:

AF XY:

0.121

AC XY:

88071

AN XY:

726570

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.394

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.0916

Gnomad4 NFE exome

AF:

0.0986

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.128

AC:

19400

AN:

152066

Hom.:

1712

Cov.:

AF XY:

0.134

AC XY:

9982

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.373

Gnomad4 SAS

AF:

0.176

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0926

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.105

Hom.:

208

Bravo

AF:

0.142

Asia WGS

AF:

0.235

AC:

816

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -

Hereditary pulmonary alveolar proteinosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2015

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

-0.88

Cadd

Benign

1.8

Dann

Benign

0.36

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