chr16-16136433-G-A

Variant names:

• chr16-16136433-G-A
• rs212087
• NM_004996.4:c.4126-45G>A

Variant summary

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

The NM_004996.4(ABCC1):​c.4126-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,601,180 control chromosomes in the GnomAD database, including 133,964 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 0.36 (10650 hom., cov: 31)
  • Exomes 𝑓: 0.41 (123314 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 20 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).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.4126-45G>A		intron_variant	Intron 28 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.4126-45G>A		intron_variant	Intron 28 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54190 AN: 151832 Hom.: 10645 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.388 AC: 92966 AN: 239692 AF XY: 0.393

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.231

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.409 AC: 593200 AN: 1449230 Hom.: 123314 Cov.: 32 AF XY: 0.409 AC XY: 294279 AN XY: 719266

African (AFR) AF: 0.180 AC: 5965 AN: 33208

American (AMR) AF: 0.398 AC: 17495 AN: 43912

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 10802 AN: 25478

East Asian (EAS) AF: 0.262 AC: 10353 AN: 39478

South Asian (SAS) AF: 0.366 AC: 31049 AN: 84900

European-Finnish (FIN) AF: 0.427 AC: 22636 AN: 53028

Middle Eastern (MID) AF: 0.362 AC: 2067 AN: 5704

European-Non Finnish (NFE) AF: 0.425 AC: 469111 AN: 1103700

Other (OTH) AF: 0.397 AC: 23722 AN: 59822

GnomAD4 genome AF: 0.357 AC: 54216 AN: 151950 Hom.: 10650 Cov.: 31 AF XY: 0.358 AC XY: 26610 AN XY: 74272

African (AFR) AF: 0.190 AC: 7863 AN: 41448

American (AMR) AF: 0.421 AC: 6426 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3468

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1770 AN: 4818

European-Finnish (FIN) AF: 0.443 AC: 4669 AN: 10544

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29391 AN: 67926

Other (OTH) AF: 0.372 AC: 784 AN: 2110

Alfa AF: 0.405 Hom.: 20453

Bravo AF: 0.342

Asia WGS AF: 0.365 AC: 1270 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	0.15
DANN	Benign	0.57
PhyloP100		-1.8
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: rs212087; hg19: chr16-16230290; COSMIC: COSV60686191;