Genetic Variant ABCC1:c.2461-30C>G (chr16-16090375-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004996.4(ABCC1):c.2461-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,551,904 control chromosomes in the GnomAD database, including 540,725 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.83 ( 51982 hom., cov: 34)

Exomes 𝑓: 0.83 ( 488743 hom. )

Consequence

ABCC1
NM_004996.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.787

Variant links:

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) 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, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ABCC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.2461-30C>G		intron_variant	Intron 18 of 30	ENST00000399410.8	NP_004987.2	P33527-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8 link	c.2461-30C>G		intron_variant	Intron 18 of 30	1	NM_004996.4	ENSP00000382342.3		P33527-1

Frequencies

GnomAD3 genomes

AF:

0.826

AC:

125640

AN:

152112

Hom.:

51954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.819

Gnomad AMI

AF:

0.908

Gnomad AMR

AF:

0.802

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.685

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.846

Gnomad OTH

AF:

0.801

GnomAD3 exomes

AF:

0.812

AC:

166372

AN:

204952

Hom.:

67783

AF XY:

0.807

AC XY:

88030

AN XY:

109058

show subpopulations

Gnomad AFR exome

AF:

0.816

Gnomad AMR exome

AF:

0.787

Gnomad ASJ exome

AF:

0.772

Gnomad EAS exome

AF:

0.823

Gnomad SAS exome

AF:

0.682

Gnomad FIN exome

AF:

0.845

Gnomad NFE exome

AF:

0.843

Gnomad OTH exome

AF:

0.813

GnomAD4 exome

AF:

0.834

AC:

1167863

AN:

1399674

Hom.:

488743

Cov.:

AF XY:

0.830

AC XY:

570996

AN XY:

688106

show subpopulations

Gnomad4 AFR exome

AF:

0.807

Gnomad4 AMR exome

AF:

0.790

Gnomad4 ASJ exome

AF:

0.769

Gnomad4 EAS exome

AF:

0.788

Gnomad4 SAS exome

AF:

0.686

Gnomad4 FIN exome

AF:

0.844

Gnomad4 NFE exome

AF:

0.851

Gnomad4 OTH exome

AF:

0.819

GnomAD4 genome

AF:

0.826

AC:

125717

AN:

152230

Hom.:

51982

Cov.:

AF XY:

0.821

AC XY:

61142

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.819

Gnomad4 AMR

AF:

0.801

Gnomad4 ASJ

AF:

0.775

Gnomad4 EAS

AF:

0.823

Gnomad4 SAS

AF:

0.683

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.846

Gnomad4 OTH

AF:

0.796

Alfa

AF:

0.825

Hom.:

9589

Bravo

AF:

0.823

Asia WGS

AF:

0.754

AC:

2625

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.2

DANN

Benign

0.39

BranchPoint Hunter

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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