rs246221

Variant names:

• chr16-16044465-T-C
• rs246221
• NM_004996.4:c.825T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-16044465-T-C
• chr16-16044465-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004996.4(ABCC1):​c.825T>C​(p.Val275Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,612,872 control chromosomes in the GnomAD database, including 88,479 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 0.41 (14303 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74176 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 73 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.825T>C	p.Val275Val	synonymous_variant	Exon 8 of 31	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.825T>C	p.Val275Val	synonymous_variant	Exon 8 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61715 AN: 151988 Hom.: 14273 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.378

GnomAD2 exomes AF: 0.333 AC: 82607 AN: 247936 AF XY: 0.320

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.305

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.311 AC: 453976 AN: 1460766 Hom.: 74176 Cov.: 37 AF XY: 0.306 AC XY: 222661 AN XY: 726720

African (AFR) AF: 0.656 AC: 21935 AN: 33454

American (AMR) AF: 0.349 AC: 15623 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 8491 AN: 26132

East Asian (EAS) AF: 0.415 AC: 16481 AN: 39690

South Asian (SAS) AF: 0.206 AC: 17748 AN: 86238

European-Finnish (FIN) AF: 0.343 AC: 18325 AN: 53410

Middle Eastern (MID) AF: 0.320 AC: 1824 AN: 5708

European-Non Finnish (NFE) AF: 0.301 AC: 334324 AN: 1111076

Other (OTH) AF: 0.319 AC: 19225 AN: 60354

GnomAD4 genome AF: 0.406 AC: 61794 AN: 152106 Hom.: 14303 Cov.: 32 AF XY: 0.405 AC XY: 30090 AN XY: 74358

African (AFR) AF: 0.644 AC: 26704 AN: 41488

American (AMR) AF: 0.343 AC: 5240 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2187 AN: 5158

South Asian (SAS) AF: 0.198 AC: 957 AN: 4828

European-Finnish (FIN) AF: 0.340 AC: 3604 AN: 10588

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20543 AN: 67978

Other (OTH) AF: 0.375 AC: 793 AN: 2114

Alfa AF: 0.332 Hom.: 43915

Bravo AF: 0.423

Asia WGS AF: 0.328 AC: 1140 AN: 3478

EpiCase AF: 0.308

EpiControl AF: 0.313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.31
DANN	Benign	0.49
PhyloP100		-1.9
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs246221; hg19: chr16-16138322; COSMIC: COSV107406339;