16-15949317-C-G

Variant names:

• chr16-15949317-C-G
• rs504348
• ENST00000574224.2:n.123+57C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000574224.2(ABCC1):​n.123+57C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 151,746 control chromosomes in the GnomAD database, including 40,677 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 0.70 (40677 hom., cov: 28)
• Consequence: ABCC1 ENST00000574224.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 12 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):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 77

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

LOC107984869 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000574224.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000574224.2	TSL:1	n.123+57C>G		intron	N/A
	ABCC1	ENST00000914139.1		c.-435C>G		upstream_gene	N/A	ENSP00000584198.1
	ABCC1	ENST00000958971.1		c.-435C>G		upstream_gene	N/A	ENSP00000629030.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 106830 AN: 151630 Hom.: 40663 Cov.: 28

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.704 AC: 106885 AN: 151746 Hom.: 40677 Cov.: 28 AF XY: 0.709 AC XY: 52543 AN XY: 74142

African (AFR) AF: 0.386 AC: 15973 AN: 41382

American (AMR) AF: 0.788 AC: 12013 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2775 AN: 3464

East Asian (EAS) AF: 0.994 AC: 5086 AN: 5116

South Asian (SAS) AF: 0.855 AC: 4117 AN: 4818

European-Finnish (FIN) AF: 0.822 AC: 8661 AN: 10536

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55890 AN: 67874

Other (OTH) AF: 0.719 AC: 1514 AN: 2106

Alfa AF: 0.697 Hom.: 2457

Bravo AF: 0.689

Asia WGS AF: 0.885 AC: 3077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.6
DANN	Benign	0.37
PhyloP100		-0.11
PromoterAI		0.050	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs504348; hg19: chr16-16043174;