rs3842375

Variant names:

• chr17-69149049-TGA-T
• rs3842375
• NM_001377321.1:c.4515_4516delTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001377321.1(ABCA10):​c.4515_4516delTC​(p.Gln1506GlyfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 1,613,668 control chromosomes in the GnomAD database, including 3,740 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (535 hom., cov: 31)
  • Exomes 𝑓: 0.060 (3205 hom.)
• Consequence: ABCA10 NM_001377321.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.83
• Publications: 11 publications found

Genes affected

ABCA10 (HGNC:30): (ATP binding cassette subfamily A member 10) 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, and White). This encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24, but neither the substrate nor the function of this gene is known. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-69149049-TGA-T is Benign according to our data. Variant chr17-69149049-TGA-T is described in ClinVar as Benign. ClinVar VariationId is 402329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA10	NM_001377321.1	c.4515_4516delTC	p.Gln1506GlyfsTer12	frameshift_variant	Exon 38 of 39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4	c.4515_4516delTC	p.Gln1506GlyfsTer12	frameshift_variant	Exon 39 of 40		NP_525021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA10	ENST00000690296.1	c.4515_4516delTC	p.Gln1506GlyfsTer12	frameshift_variant	Exon 38 of 39		NM_001377321.1	ENSP00000509702.1
ABCA10	ENST00000522406.5	n.*3443_*3444delTC		non_coding_transcript_exon_variant	Exon 40 of 41	1		ENSP00000429853.1
ABCA10	ENST00000522406.5	n.*3443_*3444delTC		3_prime_UTR_variant	Exon 40 of 41	1		ENSP00000429853.1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11064 AN: 152142 Hom.: 535 Cov.: 31

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0802

GnomAD2 exomes AF: 0.0809 AC: 20332 AN: 251264 AF XY: 0.0757

Gnomad AFR exome AF: 0.0744

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.0658

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.0871

Gnomad NFE exome AF: 0.0505

Gnomad OTH exome AF: 0.0752

GnomAD4 exome AF: 0.0601 AC: 87815 AN: 1461408 Hom.: 3205 AF XY: 0.0596 AC XY: 43314 AN XY: 727038

African (AFR) AF: 0.0734 AC: 2457 AN: 33458

American (AMR) AF: 0.165 AC: 7388 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0630 AC: 1647 AN: 26126

East Asian (EAS) AF: 0.118 AC: 4689 AN: 39678

South Asian (SAS) AF: 0.0688 AC: 5934 AN: 86222

European-Finnish (FIN) AF: 0.0851 AC: 4545 AN: 53418

Middle Eastern (MID) AF: 0.0737 AC: 425 AN: 5766

European-Non Finnish (NFE) AF: 0.0510 AC: 56729 AN: 1111670

Other (OTH) AF: 0.0663 AC: 4001 AN: 60368

GnomAD4 genome AF: 0.0728 AC: 11084 AN: 152260 Hom.: 535 Cov.: 31 AF XY: 0.0765 AC XY: 5699 AN XY: 74458

African (AFR) AF: 0.0710 AC: 2949 AN: 41554

American (AMR) AF: 0.153 AC: 2340 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3472

East Asian (EAS) AF: 0.121 AC: 625 AN: 5180

South Asian (SAS) AF: 0.0680 AC: 328 AN: 4824

European-Finnish (FIN) AF: 0.0787 AC: 835 AN: 10604

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3553 AN: 68018

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

Alfa AF: 0.0610 Hom.: 65

Bravo AF: 0.0788

Asia WGS AF: 0.0910 AC: 318 AN: 3478

EpiCase AF: 0.0508

EpiControl AF: 0.0522

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (EUR):437/8254= 5.2% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8
Mutation Taster		=145/55	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3842375; hg19: chr17-67145190; COSMIC: COSV52219404;