16-16076620-G-T

Variant names:

• chr16-16076620-G-T
• rs4148350
• NM_004996.4:c.1988+219G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 77

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004996.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.1988+219G>T		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.1862+219G>T		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.1841+219G>T		intron	N/A	NP_063957.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.1988+219G>T		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.1988+219G>T		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000399408.7	TSL:5	c.1988+219G>T		intron	N/A	ENSP00000382340.4

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

African (AFR) AF: 0.108 AC: 4495 AN: 41516

American (AMR) AF: 0.0875 AC: 1338 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0585 AC: 203 AN: 3472

East Asian (EAS) AF: 0.0501 AC: 259 AN: 5174

South Asian (SAS) AF: 0.0224 AC: 108 AN: 4828

European-Finnish (FIN) AF: 0.0677 AC: 718 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0584 AC: 3974 AN: 68022

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0664 Hom.: 821

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

Feb 01, 2014

Research Lab, National Institute of Public Health

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.57
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4148350; hg19: chr16-16170477;