chr16-16076620-G-T

Position:

• chr16-16076620-G-T

Variant summary

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

The NM_004996.4(ABCC1):​c.1988+219G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 152,226 control chromosomes in the GnomAD database, including 456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.074 (456 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.972

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.1988+219G>T		intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.1988+219G>T		intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11297 AN: 152106 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0743 AC: 11312 AN: 152226 Hom.: 456 Cov.: 32 AF XY: 0.0739 AC XY: 5504 AN XY: 74440

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0875

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0501

Gnomad4 SAS AF: 0.0224

Gnomad4 FIN AF: 0.0677

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0614 Hom.: 458

Bravo AF: 0.0802

Asia WGS AF: 0.0510 AC: 181 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial cancer of breast Uncertain:1

Uncertain significance, no assertion criteria provided

research

Research Lab, National Institute of Public Health

Feb 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.57

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: rs4148350; hg19: chr16-16170477;