16-16074751-C-T

Variant names:

• chr16-16074751-C-T
• rs35621
• NM_004996.4:c.1913-1575C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004996.4(ABCC1):​c.1913-1575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,152 control chromosomes in the GnomAD database, including 980 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 0.11 (980 hom., cov: 33)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 17 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):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 77

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.1913-1575C>T		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.1787-1575C>T		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.1766-1575C>T		intron	N/A	NP_063957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.1913-1575C>T		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.1913-1575C>T		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000914156.1		c.2069-1575C>T		intron	N/A	ENSP00000584215.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16587 AN: 152036 Hom.: 976 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.109 AC: 16605 AN: 152152 Hom.: 980 Cov.: 33 AF XY: 0.110 AC XY: 8171 AN XY: 74364

African (AFR) AF: 0.106 AC: 4412 AN: 41516

American (AMR) AF: 0.0851 AC: 1302 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3470

East Asian (EAS) AF: 0.219 AC: 1128 AN: 5162

South Asian (SAS) AF: 0.110 AC: 533 AN: 4824

European-Finnish (FIN) AF: 0.0795 AC: 841 AN: 10574

Middle Eastern (MID) AF: 0.124 AC: 36 AN: 290

European-Non Finnish (NFE) AF: 0.111 AC: 7549 AN: 68002

Other (OTH) AF: 0.109 AC: 230 AN: 2110

Alfa AF: 0.102 Hom.: 1663

Bravo AF: 0.109

Asia WGS AF: 0.186 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.67
PhyloP100		0.067
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: rs35621; hg19: chr16-16168608;