chr16-15955776-T-G

Variant names:

• chr16-15955776-T-G
• rs4781699
• NM_004996.4:c.48+5977T>G

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+5977T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,950 control chromosomes in the GnomAD database, including 33,124 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 0.66 (33124 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.732 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.48+5977T>G		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.48+5977T>G		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.48+5977T>G		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.48+5977T>G		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.48+5977T>G		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000574224.2	TSL:1	n.123+6516T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99756 AN: 151832 Hom.: 33096 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.657 AC: 99830 AN: 151950 Hom.: 33124 Cov.: 32 AF XY: 0.654 AC XY: 48559 AN XY: 74256

African (AFR) AF: 0.557 AC: 23063 AN: 41422

American (AMR) AF: 0.640 AC: 9759 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2302 AN: 3472

East Asian (EAS) AF: 0.708 AC: 3657 AN: 5164

South Asian (SAS) AF: 0.752 AC: 3625 AN: 4820

European-Finnish (FIN) AF: 0.647 AC: 6818 AN: 10540

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48561 AN: 67972

Other (OTH) AF: 0.663 AC: 1400 AN: 2112

Alfa AF: 0.692 Hom.: 68616

Bravo AF: 0.649

Asia WGS AF: 0.715 AC: 2488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.65
PhyloP100		0.39
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: rs4781699; hg19: chr16-16049633;