16-16036634-G-T

Variant names:

• chr16-16036634-G-T
• rs45609533
• NM_004996.4:c.809+31G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004996.4(ABCC1):​c.809+31G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,608,392 control chromosomes in the GnomAD database, including 163 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 0.0085 (10 hom., cov: 32)
  • Exomes 𝑓: 0.013 (153 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315
• Publications: 3 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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0128 (18655/1456020) while in subpopulation NFE AF = 0.0155 (17166/1108412). AF 95% confidence interval is 0.0153. There are 153 homozygotes in GnomAdExome4. There are 8971 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1291 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.809+31G>T		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+31G>T		intron_variant	Intron 7 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.00849 AC: 1293 AN: 152254 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00260

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00813 AC: 1980 AN: 243414 AF XY: 0.00830

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.000419

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00552

Gnomad NFE exome AF: 0.0144

Gnomad OTH exome AF: 0.00682

GnomAD4 exome AF: 0.0128 AC: 18655 AN: 1456020 Hom.: 153 Cov.: 31 AF XY: 0.0124 AC XY: 8971 AN XY: 724186

African (AFR) AF: 0.00269 AC: 90 AN: 33400

American (AMR) AF: 0.00299 AC: 133 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.000311 AC: 8 AN: 25714

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39594

South Asian (SAS) AF: 0.00330 AC: 282 AN: 85342

European-Finnish (FIN) AF: 0.00594 AC: 316 AN: 53198

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5742

European-Non Finnish (NFE) AF: 0.0155 AC: 17166 AN: 1108412

Other (OTH) AF: 0.0108 AC: 652 AN: 60196

GnomAD4 genome AF: 0.00847 AC: 1291 AN: 152372 Hom.: 10 Cov.: 32 AF XY: 0.00752 AC XY: 560 AN XY: 74516

African (AFR) AF: 0.00260 AC: 108 AN: 41586

American (AMR) AF: 0.00300 AC: 46 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4832

European-Finnish (FIN) AF: 0.00631 AC: 67 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1038 AN: 68036

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00896 Hom.: 1

Bravo AF: 0.00751

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.30
DANN	Benign	0.70
PhyloP100		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs45609533; hg19: chr16-16130491;