rs215100

Variant names:

• chr16-15960793-G-A
• rs215100
• NM_004996.4:c.48+10994G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-15960793-G-A
• chr16-15960793-G-C
• chr16-15960793-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.48+10994G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,798 control chromosomes in the GnomAD database, including 29,368 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 0.61 (29368 hom., cov: 30)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 7 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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.48+10994G>A		intron_variant	Intron 1 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.48+10994G>A		intron_variant	Intron 1 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93227 AN: 151678 Hom.: 29359 Cov.: 30

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.614 AC: 93262 AN: 151798 Hom.: 29368 Cov.: 30 AF XY: 0.610 AC XY: 45242 AN XY: 74150

African (AFR) AF: 0.471 AC: 19488 AN: 41374

American (AMR) AF: 0.610 AC: 9283 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2229 AN: 3472

East Asian (EAS) AF: 0.649 AC: 3344 AN: 5156

South Asian (SAS) AF: 0.635 AC: 3058 AN: 4814

European-Finnish (FIN) AF: 0.644 AC: 6772 AN: 10516

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47184 AN: 67942

Other (OTH) AF: 0.620 AC: 1301 AN: 2100

Alfa AF: 0.664 Hom.: 56286

Bravo AF: 0.604

Asia WGS AF: 0.639 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.1
DANN	Benign	0.70
PhyloP100		0.56
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: rs215100; hg19: chr16-16054650;