NM_004996.4:c.677+1391T>C

Variant names:

• chr16-16034561-T-C
• rs16967126
• NM_004996.4:c.677+1391T>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.677+1391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 149,650 control chromosomes in the GnomAD database, including 1,562 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 0.12 (1562 hom., cov: 28)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 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.677+1391T>C		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.551+1391T>C		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.677+1391T>C		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.677+1391T>C		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.677+1391T>C		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000574224.2	TSL:1	n.752+1391T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18212 AN: 149558 Hom.: 1553 Cov.: 28

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.00991

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.122 AC: 18239 AN: 149650 Hom.: 1562 Cov.: 28 AF XY: 0.118 AC XY: 8648 AN XY: 73020

African (AFR) AF: 0.231 AC: 9278 AN: 40242

American (AMR) AF: 0.0804 AC: 1197 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3462

East Asian (EAS) AF: 0.0378 AC: 194 AN: 5138

South Asian (SAS) AF: 0.105 AC: 500 AN: 4758

European-Finnish (FIN) AF: 0.0271 AC: 276 AN: 10168

Middle Eastern (MID) AF: 0.148 AC: 43 AN: 290

European-Non Finnish (NFE) AF: 0.0884 AC: 5987 AN: 67720

Other (OTH) AF: 0.139 AC: 288 AN: 2078

Alfa AF: 0.101 Hom.: 3845

Bravo AF: 0.133

Asia WGS AF: 0.0960 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.71
PhyloP100		0.29
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: rs16967126; hg19: chr16-16128418;