rs35587

Variant names:

• chr16-16045857-T-C
• rs35587
• NM_004996.4:c.1062T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-16045857-T-C
• chr16-16045857-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.1062T>C​(p.Asn354Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,613,574 control chromosomes in the GnomAD database, including 87,235 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 0.40 (14193 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73042 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88
• Publications: 32 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)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-3.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.1062T>C	p.Asn354Asn	synonymous	Exon 9 of 31	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.936T>C	p.Asn312Asn	synonymous	Exon 8 of 30	NP_063956.2
	ABCC1	NM_019902.2		c.1062T>C	p.Asn354Asn	synonymous	Exon 9 of 30	NP_063957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.1062T>C	p.Asn354Asn	synonymous	Exon 9 of 31	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.1062T>C	p.Asn354Asn	synonymous	Exon 9 of 30	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000574224.2	TSL:1	n.1137T>C		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61352 AN: 151940 Hom.: 14162 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.331 AC: 82189 AN: 248262 AF XY: 0.318

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.308 AC: 450630 AN: 1461516 Hom.: 73042 Cov.: 41 AF XY: 0.304 AC XY: 221058 AN XY: 727058

African (AFR) AF: 0.656 AC: 21950 AN: 33476

American (AMR) AF: 0.346 AC: 15446 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8465 AN: 26130

East Asian (EAS) AF: 0.415 AC: 16470 AN: 39698

South Asian (SAS) AF: 0.206 AC: 17773 AN: 86230

European-Finnish (FIN) AF: 0.341 AC: 18196 AN: 53394

Middle Eastern (MID) AF: 0.319 AC: 1838 AN: 5768

European-Non Finnish (NFE) AF: 0.298 AC: 331380 AN: 1111760

Other (OTH) AF: 0.316 AC: 19112 AN: 60386

GnomAD4 genome AF: 0.404 AC: 61434 AN: 152058 Hom.: 14193 Cov.: 32 AF XY: 0.402 AC XY: 29910 AN XY: 74326

African (AFR) AF: 0.643 AC: 26667 AN: 41458

American (AMR) AF: 0.337 AC: 5145 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1107 AN: 3464

East Asian (EAS) AF: 0.423 AC: 2187 AN: 5170

South Asian (SAS) AF: 0.199 AC: 961 AN: 4826

European-Finnish (FIN) AF: 0.338 AC: 3572 AN: 10582

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20355 AN: 67978

Other (OTH) AF: 0.372 AC: 787 AN: 2114

Alfa AF: 0.328 Hom.: 27148

Bravo AF: 0.421

Asia WGS AF: 0.329 AC: 1145 AN: 3478

EpiCase AF: 0.305

EpiControl AF: 0.310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.024
DANN	Benign	0.37
PhyloP100		-3.9
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: rs35587; hg19: chr16-16139714; COSMIC: COSV60680042;