rs9394952

Variant names:

• chr6-43433367-G-A
• rs9394952
• NM_001198934.2:c.1380+7G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-43433367-G-A
• chr6-43433367-G-C

Variant summary

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

The NM_001198934.2(ABCC10):​c.1380+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,595,784 control chromosomes in the GnomAD database, including 182,701 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (13434 hom., cov: 33)
  • Exomes 𝑓: 0.48 (169267 hom.)
• Consequence: ABCC10 NM_001198934.2 splice_region, intron
• Scores: Splicing: ADA: 0.00001586
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC10	NM_001198934.2	c.1380+7G>A		splice_region_variant, intron_variant	Intron 3 of 21	ENST00000372530.9	NP_001185863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC10	ENST00000372530.9	c.1380+7G>A		splice_region_variant, intron_variant	Intron 3 of 21	2	NM_001198934.2	ENSP00000361608.4
ABCC10	ENST00000244533.7	c.1251+7G>A		splice_region_variant, intron_variant	Intron 1 of 19	1		ENSP00000244533.3
ABCC10	ENST00000372515.9	c.48+7G>A		splice_region_variant, intron_variant	Intron 2 of 7	5		ENSP00000361593.4
ABCC10	ENST00000443426.2	n.238+7G>A		splice_region_variant, intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57677 AN: 152012 Hom.: 13441 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.382

GnomAD2 exomes AF: 0.463 AC: 109111 AN: 235546 AF XY: 0.469

Gnomad AFR exome AF: 0.0889

Gnomad AMR exome AF: 0.424

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.657

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.478 AC: 690487 AN: 1443654 Hom.: 169267 Cov.: 58 AF XY: 0.478 AC XY: 341889 AN XY: 715280

African (AFR) AF: 0.0850 AC: 2819 AN: 33182

American (AMR) AF: 0.420 AC: 18362 AN: 43690

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 11991 AN: 25324

East Asian (EAS) AF: 0.638 AC: 25109 AN: 39344

South Asian (SAS) AF: 0.443 AC: 37430 AN: 84510

European-Finnish (FIN) AF: 0.557 AC: 29302 AN: 52634

Middle Eastern (MID) AF: 0.344 AC: 1950 AN: 5664

European-Non Finnish (NFE) AF: 0.488 AC: 536253 AN: 1099740

Other (OTH) AF: 0.458 AC: 27271 AN: 59566

GnomAD4 genome AF: 0.379 AC: 57672 AN: 152130 Hom.: 13434 Cov.: 33 AF XY: 0.385 AC XY: 28590 AN XY: 74354

African (AFR) AF: 0.101 AC: 4175 AN: 41520

American (AMR) AF: 0.402 AC: 6150 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1566 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3249 AN: 5164

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4822

European-Finnish (FIN) AF: 0.558 AC: 5906 AN: 10578

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.485 AC: 32959 AN: 67972

Other (OTH) AF: 0.385 AC: 812 AN: 2108

Alfa AF: 0.440 Hom.: 53458

Bravo AF: 0.356

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.44
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.61		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.61		Position offset: 1

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

Other links and lift over

dbSNP: rs9394952; hg19: chr6-43401105; COSMIC: COSV55091964; COSMIC: COSV55091964;