chr16-16068119-G-A

Variant names:

• chr16-16068119-G-A
• rs35604
• NM_004996.4:c.1678-37G>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.1678-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 1,611,314 control chromosomes in the GnomAD database, including 540,370 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 0.83 (52447 hom., cov: 32)
  • Exomes 𝑓: 0.82 (487923 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.03
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 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.1678-37G>A		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.1552-37G>A		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.1678-3523G>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.1678-37G>A		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.1678-37G>A		intron	N/A	ENSP00000461615.2
	ABCC1	ENST00000399408.7	TSL:5	c.1678-37G>A		intron	N/A	ENSP00000382340.4

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126030 AN: 152054 Hom.: 52411 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.803

GnomAD2 exomes AF: 0.791 AC: 195821 AN: 247594 AF XY: 0.783

Gnomad AFR exome AF: 0.870

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.767

Gnomad EAS exome AF: 0.790

Gnomad FIN exome AF: 0.838

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.796

GnomAD4 exome AF: 0.816 AC: 1189938 AN: 1459142 Hom.: 487923 Cov.: 41 AF XY: 0.809 AC XY: 587212 AN XY: 725826

African (AFR) AF: 0.865 AC: 28955 AN: 33458

American (AMR) AF: 0.780 AC: 34816 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 20013 AN: 26110

East Asian (EAS) AF: 0.771 AC: 30596 AN: 39664

South Asian (SAS) AF: 0.614 AC: 52936 AN: 86184

European-Finnish (FIN) AF: 0.836 AC: 43921 AN: 52536

Middle Eastern (MID) AF: 0.759 AC: 4366 AN: 5756

European-Non Finnish (NFE) AF: 0.834 AC: 925754 AN: 1110470

Other (OTH) AF: 0.806 AC: 48581 AN: 60302

GnomAD4 genome AF: 0.829 AC: 126113 AN: 152172 Hom.: 52447 Cov.: 32 AF XY: 0.823 AC XY: 61239 AN XY: 74394

African (AFR) AF: 0.869 AC: 36073 AN: 41516

American (AMR) AF: 0.799 AC: 12200 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2690 AN: 3466

East Asian (EAS) AF: 0.796 AC: 4120 AN: 5174

South Asian (SAS) AF: 0.612 AC: 2950 AN: 4818

European-Finnish (FIN) AF: 0.837 AC: 8878 AN: 10608

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.831 AC: 56490 AN: 67996

Other (OTH) AF: 0.797 AC: 1685 AN: 2114

Alfa AF: 0.816 Hom.: 66370

Bravo AF: 0.829

Asia WGS AF: 0.715 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.024
DANN	Benign	0.76
PhyloP100		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs35604; hg19: chr16-16161976;