Genetic Variant NM_001198934.2:c.1380+7G>A (chr6-43433367-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Variant links:

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]

ABCC10 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
ABCC10	NM_001198934.2 link	c.1380+7G>A		splice_region_variant, intron_variant	Intron 3 of 21	ENST00000372530.9	NP_001185863.1	Q5T3U5-1A0A024RD21

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCC10	ENST00000372530.9 link	c.1380+7G>A	splice_region_variant, intron_variant	Intron 3 of 21	2	NM_001198934.2	ENSP00000361608.4	Q5T3U5-1
ABCC10	ENST00000244533.7 link	c.1251+7G>A	splice_region_variant, intron_variant	Intron 1 of 19	1		ENSP00000244533.3	Q5T3U5-2
ABCC10	ENST00000372515.8 link	c.48+7G>A	splice_region_variant, intron_variant	Intron 2 of 7	5		ENSP00000361593.4	D6R9B3
ABCC10	ENST00000443426.2 link	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.478

AC XY:

341889

AN XY:

715280

show subpopulations

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.:

AF XY:

0.385

AC XY:

28590

AN XY:

74354

show subpopulations

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over