rs45492500

Variant names:

• chr16-16090378-G-A
• rs45492500
• NM_004996.4:c.2461-27G>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.2461-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,557,780 control chromosomes in the GnomAD database, including 1,907 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 0.036 (134 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1773 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• 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: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, 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 (NFE) allele frequency at 95% confidence interval = 0.0526 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.2461-27G>A		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.2335-27G>A		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.2314-27G>A		intron	N/A	NP_063957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.2461-27G>A		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.2284-27G>A		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000914156.1		c.2617-27G>A		intron	N/A	ENSP00000584215.1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5482 AN: 152186 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0335

GnomAD2 exomes AF: 0.0379 AC: 7980 AN: 210296 AF XY: 0.0393

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.0000590

Gnomad FIN exome AF: 0.0609

Gnomad NFE exome AF: 0.0566

Gnomad OTH exome AF: 0.0396

GnomAD4 exome AF: 0.0480 AC: 67512 AN: 1405476 Hom.: 1773 Cov.: 34 AF XY: 0.0474 AC XY: 32806 AN XY: 691886

African (AFR) AF: 0.00885 AC: 287 AN: 32420

American (AMR) AF: 0.0176 AC: 712 AN: 40556

Ashkenazi Jewish (ASJ) AF: 0.0342 AC: 787 AN: 23008

East Asian (EAS) AF: 0.0000777 AC: 3 AN: 38614

South Asian (SAS) AF: 0.0168 AC: 1308 AN: 77830

European-Finnish (FIN) AF: 0.0607 AC: 3067 AN: 50564

Middle Eastern (MID) AF: 0.0301 AC: 164 AN: 5452

European-Non Finnish (NFE) AF: 0.0544 AC: 58665 AN: 1079164

Other (OTH) AF: 0.0435 AC: 2519 AN: 57868

GnomAD4 genome AF: 0.0360 AC: 5479 AN: 152304 Hom.: 134 Cov.: 32 AF XY: 0.0344 AC XY: 2565 AN XY: 74466

African (AFR) AF: 0.0120 AC: 499 AN: 41580

American (AMR) AF: 0.0296 AC: 452 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4818

European-Finnish (FIN) AF: 0.0505 AC: 536 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0541 AC: 3680 AN: 68030

Other (OTH) AF: 0.0336 AC: 71 AN: 2114

Alfa AF: 0.114 Hom.: 965

Bravo AF: 0.0338

Asia WGS AF: 0.00924 AC: 34 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	0.0020
DANN	Benign	0.80
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs45492500; hg19: chr16-16184235;