rs2277122

Variant names:

• chr6-43438763-C-T
• rs2277122
• NM_001198934.2:c.2095C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001198934.2(ABCC10):​c.2095C>T​(p.Leu699Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,614,142 control chromosomes in the GnomAD database, including 2,701 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (213 hom., cov: 33)
  • Exomes 𝑓: 0.051 (2488 hom.)
• Consequence: ABCC10 NM_001198934.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 14 publications found

Genes affected

ABCC10 (HGNC:52): (ATP binding cassette subfamily C member 10) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This ABC full-transporter is a member of the MRP subfamily which is involved in multi-drug resistance. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP7: Synonymous conserved (PhyloP=-0.104 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC10	NM_001198934.2	c.2095C>T	p.Leu699Leu	synonymous_variant	Exon 8 of 22	ENST00000372530.9	NP_001185863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC10	ENST00000372530.9	c.2095C>T	p.Leu699Leu	synonymous_variant	Exon 8 of 22	2	NM_001198934.2	ENSP00000361608.4

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6248 AN: 152166 Hom.: 214 Cov.: 33

Gnomad AFR AF: 0.00924

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0649 AC: 16326 AN: 251418 AF XY: 0.0666

Gnomad AFR exome AF: 0.00695

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.0503

Gnomad EAS exome AF: 0.106

Gnomad FIN exome AF: 0.0316

Gnomad NFE exome AF: 0.0444

Gnomad OTH exome AF: 0.0598

GnomAD4 exome AF: 0.0507 AC: 74057 AN: 1461858 Hom.: 2488 Cov.: 31 AF XY: 0.0527 AC XY: 38293 AN XY: 727244

African (AFR) AF: 0.00699 AC: 234 AN: 33480

American (AMR) AF: 0.0970 AC: 4337 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0504 AC: 1317 AN: 26134

East Asian (EAS) AF: 0.111 AC: 4407 AN: 39700

South Asian (SAS) AF: 0.128 AC: 11032 AN: 86258

European-Finnish (FIN) AF: 0.0329 AC: 1757 AN: 53416

Middle Eastern (MID) AF: 0.0759 AC: 438 AN: 5768

European-Non Finnish (NFE) AF: 0.0426 AC: 47342 AN: 1111986

Other (OTH) AF: 0.0529 AC: 3193 AN: 60396

GnomAD4 genome AF: 0.0410 AC: 6247 AN: 152284 Hom.: 213 Cov.: 33 AF XY: 0.0433 AC XY: 3228 AN XY: 74466

African (AFR) AF: 0.00921 AC: 383 AN: 41574

American (AMR) AF: 0.0684 AC: 1046 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3468

East Asian (EAS) AF: 0.113 AC: 585 AN: 5172

South Asian (SAS) AF: 0.142 AC: 683 AN: 4824

European-Finnish (FIN) AF: 0.0317 AC: 337 AN: 10626

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0426 AC: 2896 AN: 68004

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

Alfa AF: 0.0448 Hom.: 591

Bravo AF: 0.0410

Asia WGS AF: 0.119 AC: 413 AN: 3478

EpiCase AF: 0.0480

EpiControl AF: 0.0484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.4
DANN	Benign	0.74
PhyloP100		-0.10
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: rs2277122; hg19: chr6-43406501;