Genetic Variant ABCC1:c.1218+8A>G (chr16-16046021-A-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.1218+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,612,758 control chromosomes in the GnomAD database, including 85,821 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 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 0.40 ( 13561 hom., cov: 32)

Exomes 𝑓: 0.31 ( 72260 hom. )

Consequence

ABCC1
NM_004996.4 splice_region, intron

Scores

Splicing: ADA: 0.000007049

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.40

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

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.1218+8A>G		splice_region_variant, intron_variant	Intron 9 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.1218+8A>G		splice_region_variant, intron_variant	Intron 9 of 30	1	NM_004996.4	ENSP00000382342.3		P33527-1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60316

AN:

151862

Hom.:

13533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.335

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.368

GnomAD3 exomes

AF:

0.328

AC:

81188

AN:

247250

Hom.:

14536

AF XY:

0.316

AC XY:

42339

AN XY:

134136

show subpopulations

Gnomad AFR exome

AF:

0.632

Gnomad AMR exome

AF:

0.346

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.426

Gnomad SAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.307

AC:

448891

AN:

1460780

Hom.:

72260

Cov.:

AF XY:

0.303

AC XY:

220171

AN XY:

726608

show subpopulations

Gnomad4 AFR exome

AF:

0.631

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.415

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.397

AC:

60395

AN:

151978

Hom.:

13561

Cov.:

AF XY:

0.396

AC XY:

29433

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.621

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.349

Hom.:

4692

Bravo

AF:

0.413

Asia WGS

AF:

0.329

AC:

1143

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.32

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000070

dbscSNV1_RF

Benign

0.0

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