16-16088099-T-C

Variant names:

• chr16-16088099-T-C
• rs2889517
• NM_004996.4:c.2460+1108T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004996.4(ABCC1):​c.2460+1108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,856 control chromosomes in the GnomAD database, including 31,469 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 0.64 (31469 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.2460+1108T>C		intron_variant	Intron 18 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.2460+1108T>C		intron_variant	Intron 18 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97240 AN: 151738 Hom.: 31466 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.641 AC: 97279 AN: 151856 Hom.: 31469 Cov.: 32 AF XY: 0.632 AC XY: 46936 AN XY: 74222

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.605

Alfa AF: 0.675 Hom.: 33872

Bravo AF: 0.637

Asia WGS AF: 0.544 AC: 1889 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs2889517; hg19: chr16-16181956;