rs9394952

chr6-43433367-G-Achr6-43433367-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ABCC10	NM_001198934.2	c.1380+7G>A		splice_region_variant, intron_variant		ENST00000372530.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC10	ENST00000372530.9	c.1380+7G>A		splice_region_variant, intron_variant		2	NM_001198934.2	P2
ABCC10	ENST00000244533.7	c.1251+7G>A		splice_region_variant, intron_variant		1		A2
ABCC10	ENST00000372515.8	c.48+7G>A		splice_region_variant, intron_variant		5
ABCC10	ENST00000443426.2	n.238+7G>A		splice_region_variant, intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.463 AC: 109111 AN: 235546 Hom.: 26743 AF XY: 0.469 AC XY: 59736 AN XY: 127388

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 SAS exome AF: 0.449

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

Gnomad4 AFR exome AF: 0.0850

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.474

Gnomad4 EAS exome AF: 0.638

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.458

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

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.385

Alfa AF: 0.448 Hom.: 24913

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

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