rs13332547

Variant names:

• chr16-2317423-G-A
• rs13332547
• NM_001089.3:c.991-20C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2317423-G-A
• chr16-2317423-G-C
• chr16-2317423-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.113

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ABCA3	NM_001089.3	c.991-20C>T		intron_variant	Intron 9 of 32	ENST00000301732.10	NP_001080.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA3	ENST00000301732.10	c.991-20C>T		intron_variant	Intron 9 of 32	1	NM_001089.3	ENSP00000301732.5
ABCA3	ENST00000382381.7	c.991-20C>T		intron_variant	Intron 9 of 31	1		ENSP00000371818.3
ABCA3	ENST00000563623.5	n.1554-20C>T		intron_variant	Intron 9 of 19	1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19345 AN: 151948 Hom.: 1699 Cov.: 31

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

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.: 33 AF XY: 0.121 AC XY: 88071 AN XY: 726570

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.: 31 AF XY: 0.134 AC XY: 9982 AN XY: 74336

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jul 21, 2018

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary pulmonary alveolar proteinosis Benign:1

Oct 14, 2015

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	-0.88
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

Other links and lift over

dbSNP: rs13332547; hg19: chr16-2367424; COSMIC: COSV57055826;