rs35595

Variant names:

• chr16-16056014-G-A
• rs35595
• NM_004996.4:c.1474-78G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-16056014-G-A
• chr16-16056014-G-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.1474-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,297,882 control chromosomes in the GnomAD database, including 20,742 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 0.23 (5609 hom., cov: 31)
  • Exomes 𝑓: 0.15 (15133 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• 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=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1474-78G>A		intron_variant	Intron 11 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.1474-78G>A		intron_variant	Intron 11 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35197 AN: 151760 Hom.: 5593 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.152 AC: 174175 AN: 1146004 Hom.: 15133 AF XY: 0.151 AC XY: 86943 AN XY: 576876

African (AFR) AF: 0.459 AC: 11715 AN: 25530

American (AMR) AF: 0.145 AC: 4588 AN: 31726

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3335 AN: 21222

East Asian (EAS) AF: 0.273 AC: 10228 AN: 37400

South Asian (SAS) AF: 0.141 AC: 10220 AN: 72306

European-Finnish (FIN) AF: 0.133 AC: 6580 AN: 49606

Middle Eastern (MID) AF: 0.207 AC: 1024 AN: 4938

European-Non Finnish (NFE) AF: 0.139 AC: 118405 AN: 854148

Other (OTH) AF: 0.164 AC: 8080 AN: 49128

GnomAD4 genome AF: 0.232 AC: 35253 AN: 151878 Hom.: 5609 Cov.: 31 AF XY: 0.231 AC XY: 17159 AN XY: 74234

African (AFR) AF: 0.452 AC: 18704 AN: 41336

American (AMR) AF: 0.158 AC: 2414 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1428 AN: 5166

South Asian (SAS) AF: 0.147 AC: 708 AN: 4812

European-Finnish (FIN) AF: 0.135 AC: 1419 AN: 10546

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9247 AN: 67966

Other (OTH) AF: 0.216 AC: 454 AN: 2106

Alfa AF: 0.155 Hom.: 2964

Bravo AF: 0.247

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.53
PhyloP100		-1.5
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: rs35595; hg19: chr16-16149871; COSMIC: COSV60691108;