rs4148358

Variant names:

• chr16-16093318-C-T
• rs4148358
• NM_004996.4:c.2644+2730C>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.2644+2730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,866 control chromosomes in the GnomAD database, including 4,432 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 0.24 (4432 hom., cov: 31)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 10 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 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.2644+2730C>T		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.2518+2730C>T		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.2497+2730C>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.2644+2730C>T		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.2467+2730C>T		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000914156.1		c.2800+2730C>T		intron	N/A	ENSP00000584215.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36553 AN: 151748 Hom.: 4426 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.241 AC: 36591 AN: 151866 Hom.: 4432 Cov.: 31 AF XY: 0.245 AC XY: 18196 AN XY: 74212

African (AFR) AF: 0.240 AC: 9949 AN: 41382

American (AMR) AF: 0.223 AC: 3402 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1064 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1609 AN: 5152

South Asian (SAS) AF: 0.304 AC: 1460 AN: 4808

European-Finnish (FIN) AF: 0.239 AC: 2513 AN: 10532

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15655 AN: 67948

Other (OTH) AF: 0.241 AC: 508 AN: 2106

Alfa AF: 0.230 Hom.: 6865

Bravo AF: 0.235

Asia WGS AF: 0.336 AC: 1171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.48
DANN	Benign	0.74
PhyloP100		-2.6
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: rs4148358; hg19: chr16-16187175;