chr17-69182175-A-G

Variant names:

• chr17-69182175-A-G
• rs4968849
• NM_001377321.1:c.2747T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000690296.1(ABCA10):​c.2747T>C​(p.Met916Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,581,928 control chromosomes in the GnomAD database, including 411,137 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.75 (43063 hom., cov: 30)
  • Exomes 𝑓: 0.72 (368074 hom.)
• Consequence: ABCA10 ENST00000690296.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 36 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.150353E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000690296.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA10	NM_001377321.1	MANE Select	c.2747T>C	p.Met916Thr	missense	Exon 22 of 39	NP_001364250.1
	ABCA10	NM_080282.4		c.2747T>C	p.Met916Thr	missense	Exon 23 of 40	NP_525021.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA10	ENST00000690296.1	MANE Select	c.2747T>C	p.Met916Thr	missense	Exon 22 of 39	ENSP00000509702.1
	ABCA10	ENST00000269081.8	TSL:1	c.2747T>C	p.Met916Thr	missense	Exon 23 of 40	ENSP00000269081.4
	ABCA10	ENST00000518929.5	TSL:1	n.*1793T>C		non_coding_transcript_exon	Exon 20 of 35	ENSP00000430341.1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113567 AN: 151800 Hom.: 43026 Cov.: 30

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.737

GnomAD2 exomes AF: 0.710 AC: 164354 AN: 231388 AF XY: 0.708

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.767

Gnomad ASJ exome AF: 0.607

Gnomad EAS exome AF: 0.462

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.724

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.715 AC: 1022480 AN: 1430010 Hom.: 368074 Cov.: 43 AF XY: 0.714 AC XY: 507859 AN XY: 711312

African (AFR) AF: 0.839 AC: 26711 AN: 31826

American (AMR) AF: 0.767 AC: 31709 AN: 41324

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15349 AN: 25254

East Asian (EAS) AF: 0.452 AC: 16972 AN: 37508

South Asian (SAS) AF: 0.695 AC: 56387 AN: 81094

European-Finnish (FIN) AF: 0.727 AC: 38171 AN: 52540

Middle Eastern (MID) AF: 0.757 AC: 4162 AN: 5500

European-Non Finnish (NFE) AF: 0.722 AC: 791066 AN: 1096162

Other (OTH) AF: 0.713 AC: 41953 AN: 58802

GnomAD4 genome AF: 0.748 AC: 113664 AN: 151918 Hom.: 43063 Cov.: 30 AF XY: 0.746 AC XY: 55399 AN XY: 74242

African (AFR) AF: 0.839 AC: 34807 AN: 41488

American (AMR) AF: 0.768 AC: 11716 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2101 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2382 AN: 5168

South Asian (SAS) AF: 0.684 AC: 3296 AN: 4820

European-Finnish (FIN) AF: 0.721 AC: 7583 AN: 10524

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49273 AN: 67896

Other (OTH) AF: 0.736 AC: 1547 AN: 2102

Alfa AF: 0.724 Hom.: 140654

Bravo AF: 0.753

TwinsUK AF: 0.730 AC: 2705

ALSPAC AF: 0.717 AC: 2763

ESP6500AA AF: 0.837 AC: 3688

ESP6500EA AF: 0.716 AC: 6157

ExAC AF: 0.711 AC: 86359

Asia WGS AF: 0.601 AC: 2092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.22
DANN	Benign	0.16
DEOGEN2	Benign	0.000058	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.7	N
PhyloP100		0.18
PrimateAI	Benign	0.34	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.0080
MPC		0.030
ClinPred		0.00068	T
GERP RS		0.66
Varity_R		0.026
gMVP		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4968849; hg19: chr17-67178316; COSMIC: COSV52219016;