Genetic Variant NM_001377321.1:c.4515_4516delTC (chr17-69149049-TGA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.83

Variant links:

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]

ABCA10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.4515_4516delTC	p.Gln1506GlyfsTer12	frameshift_variant	Exon 38 of 39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4 link	c.4515_4516delTC	p.Gln1506GlyfsTer12	frameshift_variant	Exon 39 of 40		NP_525021.3	Q8WWZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCA10	ENST00000690296.1 link	c.4515_4516delTC	p.Gln1506GlyfsTer12	frameshift_variant	Exon 38 of 39		NM_001377321.1	ENSP00000509702.1	Q8WWZ4-1
ABCA10	ENST00000522406.5 link	n.3443_3444delTC		non_coding_transcript_exon_variant	Exon 40 of 41	1		ENSP00000429853.1	Q8WWZ4-5
ABCA10	ENST00000522406.5 link	n.3443_3444delTC		3_prime_UTR_variant	Exon 40 of 41	1		ENSP00000429853.1	Q8WWZ4-5

Frequencies

GnomAD3 genomes

AF:

0.0727

AC:

11064

AN:

152142

Hom.:

535

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0809

AC:

20332

AN:

251264

Hom.:

1089

AF XY:

0.0757

AC XY:

10284

AN XY:

135796

show subpopulations

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 SAS exome

AF:

0.0675

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

show subpopulations

Gnomad4 AFR exome

AF:

0.0734

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.0630

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.0688

Gnomad4 FIN exome

AF:

0.0851

Gnomad4 NFE exome

AF:

0.0510

Gnomad4 OTH exome

AF:

0.0663

GnomAD4 genome

AF:

0.0728

AC:

11084

AN:

152260

Hom.:

535

Cov.:

AF XY:

0.0765

AC XY:

5699

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.121

Gnomad4 SAS

AF:

0.0680

Gnomad4 FIN

AF:

0.0787

Gnomad4 NFE

AF:

0.0522

Gnomad4 OTH

AF:

0.0827

Alfa

AF:

0.0610

Hom.:

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

LINK: link

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

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

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