rs246240

Variant names:

• chr16-16025167-A-G
• rs246240
• NM_004996.4:c.616-7942A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-16025167-A-G
• chr16-16025167-A-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.616-7942A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,068 control chromosomes in the GnomAD database, including 2,116 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 0.15 (2116 hom., cov: 31)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 35 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.616-7942A>G		intron_variant	Intron 5 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.616-7942A>G		intron_variant	Intron 5 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23304 AN: 151950 Hom.: 2114 Cov.: 31

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.153 AC: 23333 AN: 152068 Hom.: 2116 Cov.: 31 AF XY: 0.159 AC XY: 11849 AN XY: 74316

African (AFR) AF: 0.0861 AC: 3571 AN: 41492

American (AMR) AF: 0.205 AC: 3132 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3470

East Asian (EAS) AF: 0.374 AC: 1928 AN: 5156

South Asian (SAS) AF: 0.124 AC: 596 AN: 4812

European-Finnish (FIN) AF: 0.233 AC: 2465 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10518 AN: 67984

Other (OTH) AF: 0.152 AC: 322 AN: 2112

Alfa AF: 0.156 Hom.: 8852

Bravo AF: 0.153

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.071
DANN	Benign	0.33
PhyloP100		-2.1
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: rs246240; hg19: chr16-16119024;