rs246232

Variant names:

• chr16-16036667-C-G
• rs246232
• NM_004996.4:c.809+64C>G

Variant summary

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

The NM_004996.4(ABCC1):​c.809+64C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,561,274 control chromosomes in the GnomAD database, including 103,829 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 0.46 (19830 hom., cov: 33)
  • Exomes 𝑓: 0.33 (83999 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.809+64C>G		intron_variant	Intron 7 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.809+64C>G		intron_variant	Intron 7 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70375 AN: 151854 Hom.: 19781 Cov.: 33

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.335 AC: 471834 AN: 1409302 Hom.: 83999 AF XY: 0.332 AC XY: 232461 AN XY: 700628

African (AFR) AF: 0.824 AC: 26753 AN: 32476

American (AMR) AF: 0.362 AC: 15359 AN: 42380

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 9722 AN: 23996

East Asian (EAS) AF: 0.421 AC: 16335 AN: 38828

South Asian (SAS) AF: 0.281 AC: 22707 AN: 80756

European-Finnish (FIN) AF: 0.337 AC: 17580 AN: 52114

Middle Eastern (MID) AF: 0.363 AC: 2025 AN: 5580

European-Non Finnish (NFE) AF: 0.317 AC: 340755 AN: 1074718

Other (OTH) AF: 0.352 AC: 20598 AN: 58454

GnomAD4 genome AF: 0.464 AC: 70478 AN: 151972 Hom.: 19830 Cov.: 33 AF XY: 0.460 AC XY: 34170 AN XY: 74296

African (AFR) AF: 0.805 AC: 33339 AN: 41390

American (AMR) AF: 0.373 AC: 5694 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1407 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2143 AN: 5178

South Asian (SAS) AF: 0.282 AC: 1359 AN: 4826

European-Finnish (FIN) AF: 0.333 AC: 3517 AN: 10572

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21584 AN: 67954

Other (OTH) AF: 0.438 AC: 923 AN: 2108

Alfa AF: 0.406 Hom.: 1883

Bravo AF: 0.487

Asia WGS AF: 0.374 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.51
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs246232; hg19: chr16-16130524; COSMIC: COSV107406338;