6-43441680-A-G

Variant names:

• chr6-43441680-A-G
• rs2487663
• NM_001198934.2:c.2128-182A>G

Variant summary

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

The NM_001198934.2(ABCC10):​c.2128-182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,126 control chromosomes in the GnomAD database, including 41,264 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 0.73 (41264 hom., cov: 32)
• Consequence: ABCC10 NM_001198934.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198934.2. 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
	ABCC10	NM_001198934.2	MANE Select	c.2128-182A>G		intron	N/A	NP_001185863.1
	ABCC10	NM_033450.3		c.2044-182A>G		intron	N/A	NP_258261.2
	ABCC10	NM_001350518.2		c.796-182A>G		intron	N/A	NP_001337447.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC10	ENST00000372530.9	TSL:2 MANE Select	c.2128-182A>G		intron	N/A	ENSP00000361608.4
	ABCC10	ENST00000244533.7	TSL:1	c.2044-182A>G		intron	N/A	ENSP00000244533.3
	ABCC10	ENST00000921385.1		c.2173-182A>G		intron	N/A	ENSP00000591444.1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110783 AN: 152008 Hom.: 41244 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.733

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.729 AC: 110848 AN: 152126 Hom.: 41264 Cov.: 32 AF XY: 0.726 AC XY: 54012 AN XY: 74370

African (AFR) AF: 0.583 AC: 24167 AN: 41456

American (AMR) AF: 0.699 AC: 10691 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2615 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3499 AN: 5178

South Asian (SAS) AF: 0.668 AC: 3219 AN: 4822

European-Finnish (FIN) AF: 0.806 AC: 8538 AN: 10588

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55564 AN: 68014

Other (OTH) AF: 0.733 AC: 1545 AN: 2108

Alfa AF: 0.781 Hom.: 135447

Bravo AF: 0.712

Asia WGS AF: 0.667 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.72
DANN	Benign	0.48
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2487663; hg19: chr6-43409418;