NM_004996.4:c.616-3918C>A

Variant names:

• chr16-16029191-C-A
• rs875740
• NM_004996.4:c.616-3918C>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.616-3918C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,008 control chromosomes in the GnomAD database, including 27,260 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 0.59 (27260 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897
• Publications: 15 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 (NFE) allele frequency at 95% confidence interval = 0.653 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.616-3918C>A		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.490-3918C>A		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.616-3918C>A		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.616-3918C>A		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.616-3918C>A		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000574224.2	TSL:1	n.691-3918C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90314 AN: 151890 Hom.: 27254 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.594 AC: 90364 AN: 152008 Hom.: 27260 Cov.: 32 AF XY: 0.587 AC XY: 43588 AN XY: 74308

African (AFR) AF: 0.528 AC: 21873 AN: 41452

American (AMR) AF: 0.608 AC: 9294 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2192 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1941 AN: 5166

South Asian (SAS) AF: 0.472 AC: 2275 AN: 4822

European-Finnish (FIN) AF: 0.583 AC: 6152 AN: 10554

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.658 AC: 44703 AN: 67956

Other (OTH) AF: 0.602 AC: 1271 AN: 2110

Alfa AF: 0.624 Hom.: 15052

Bravo AF: 0.593

Asia WGS AF: 0.410 AC: 1429 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	0.30
DANN	Benign	0.23
PhyloP100		-0.90
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: rs875740; hg19: chr16-16123048;