16-16106899-C-T

Variant names:

• chr16-16106899-C-T
• rs11075296
• NM_004996.4:c.2871+26C>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.2871+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,752 control chromosomes in the GnomAD database, including 799,732 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 0.97 (72412 hom., cov: 31)
  • Exomes 𝑓: 1.0 (727320 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.2871+26C>T		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.2745+26C>T		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.2724+26C>T		intron	N/A	NP_063957.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.2871+26C>T		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.2694+26C>T		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000399408.7	TSL:5	c.2901+26C>T		intron	N/A	ENSP00000382340.4

Frequencies

GnomAD3 genomes AF: 0.974 AC: 148265 AN: 152146 Hom.: 72361 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.984

GnomAD2 exomes AF: 0.994 AC: 246306 AN: 247902 AF XY: 0.995

Gnomad AFR exome AF: 0.906

Gnomad AMR exome AF: 0.996

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.998

GnomAD4 exome AF: 0.998 AC: 1457943 AN: 1461488 Hom.: 727320 Cov.: 54 AF XY: 0.998 AC XY: 725556 AN XY: 727046

African (AFR) AF: 0.910 AC: 30476 AN: 33472

American (AMR) AF: 0.996 AC: 44525 AN: 44690

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26126 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39694 AN: 39694

South Asian (SAS) AF: 1.00 AC: 86222 AN: 86232

European-Finnish (FIN) AF: 1.00 AC: 53272 AN: 53272

Middle Eastern (MID) AF: 0.997 AC: 5740 AN: 5760

European-Non Finnish (NFE) AF: 1.00 AC: 1111822 AN: 1111864

Other (OTH) AF: 0.995 AC: 60066 AN: 60378

GnomAD4 genome AF: 0.974 AC: 148376 AN: 152264 Hom.: 72412 Cov.: 31 AF XY: 0.976 AC XY: 72633 AN XY: 74452

African (AFR) AF: 0.911 AC: 37845 AN: 41534

American (AMR) AF: 0.990 AC: 15144 AN: 15292

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5168 AN: 5168

South Asian (SAS) AF: 1.00 AC: 4822 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10618 AN: 10618

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68023 AN: 68036

Other (OTH) AF: 0.984 AC: 2080 AN: 2114

Alfa AF: 0.990 Hom.: 91227

Bravo AF: 0.970

Asia WGS AF: 0.994 AC: 3456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.46
PhyloP100		-0.85
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: rs11075296; hg19: chr16-16200756;