NM_004996.4:c.1677+4951A>C

Variant names:

• chr16-16061246-A-C
• rs17287570
• NM_004996.4:c.1677+4951A>C

Variant summary

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

The NM_004996.4(ABCC1):​c.1677+4951A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,162 control chromosomes in the GnomAD database, including 2,318 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 0.16 (2318 hom., cov: 33)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 10 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):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 77

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 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.1677+4951A>C		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.1551+4951A>C		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.1677+4951A>C		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.1677+4951A>C		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.1677+4951A>C		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000914156.1		c.1833+4951A>C		intron	N/A	ENSP00000584215.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24892 AN: 152044 Hom.: 2320 Cov.: 33

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.164 AC: 24890 AN: 152162 Hom.: 2318 Cov.: 33 AF XY: 0.166 AC XY: 12321 AN XY: 74364

African (AFR) AF: 0.0821 AC: 3412 AN: 41558

American (AMR) AF: 0.166 AC: 2539 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3470

East Asian (EAS) AF: 0.119 AC: 614 AN: 5174

South Asian (SAS) AF: 0.170 AC: 818 AN: 4816

European-Finnish (FIN) AF: 0.236 AC: 2492 AN: 10552

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13541 AN: 67992

Other (OTH) AF: 0.167 AC: 354 AN: 2114

Alfa AF: 0.185 Hom.: 8899

Bravo AF: 0.151

Asia WGS AF: 0.151 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.44
PhyloP100		1.3
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: rs17287570; hg19: chr16-16155103;