chr16-16015037-G-A

Variant names:

• chr16-16015037-G-A
• rs1967120
• NM_004996.4:c.489+409G>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.489+409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,904 control chromosomes in the GnomAD database, including 32,544 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 0.65 (32544 hom., cov: 31)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 14 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 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.489+409G>A		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.489+409G>A		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.489+409G>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.489+409G>A		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.489+409G>A		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000574224.2	TSL:1	n.564+409G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98633 AN: 151786 Hom.: 32533 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.650 AC: 98678 AN: 151904 Hom.: 32544 Cov.: 31 AF XY: 0.639 AC XY: 47465 AN XY: 74248

African (AFR) AF: 0.626 AC: 25906 AN: 41394

American (AMR) AF: 0.639 AC: 9751 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2358 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1888 AN: 5168

South Asian (SAS) AF: 0.468 AC: 2249 AN: 4808

European-Finnish (FIN) AF: 0.632 AC: 6659 AN: 10544

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47850 AN: 67952

Other (OTH) AF: 0.639 AC: 1349 AN: 2112

Alfa AF: 0.676 Hom.: 68250

Bravo AF: 0.647

Asia WGS AF: 0.419 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-0.16
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: rs1967120; hg19: chr16-16108894;