rs576075

Variant names:

• chr6-160264504-C-T
• rs576075
• ENST00000366952.1:c.-1296-3817G>A

Variant summary

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

The ENST00000366952.1(SLC22A2):​c.-1296-3817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,986 control chromosomes in the GnomAD database, including 5,003 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 0.25 (5003 hom., cov: 32)
• Consequence: SLC22A2 ENST00000366952.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 6 publications found

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

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 (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366952.1	c.-1296-3817G>A		intron_variant	Intron 1 of 7	5		ENSP00000355919.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37789 AN: 151872 Hom.: 5002 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.249 AC: 37802 AN: 151986 Hom.: 5003 Cov.: 32 AF XY: 0.244 AC XY: 18092 AN XY: 74276

African (AFR) AF: 0.199 AC: 8229 AN: 41432

American (AMR) AF: 0.203 AC: 3096 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3472

East Asian (EAS) AF: 0.0896 AC: 463 AN: 5168

South Asian (SAS) AF: 0.136 AC: 657 AN: 4816

European-Finnish (FIN) AF: 0.253 AC: 2662 AN: 10534

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20601 AN: 67976

Other (OTH) AF: 0.270 AC: 570 AN: 2108

Alfa AF: 0.283 Hom.: 4762

Bravo AF: 0.245

Asia WGS AF: 0.113 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.25
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs576075; hg19: chr6-160685536;