rs2457576

Variant names:

• chr6-160444587-G-C
• rs2457576
• NM_021977.4:c.1510+845G>C

Variant summary

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

The ENST00000275300.3(SLC22A3):​c.1510+845G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,854 control chromosomes in the GnomAD database, including 6,055 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 0.28 (6055 hom., cov: 31)
• Consequence: SLC22A3 ENST00000275300.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.665
• Publications: 11 publications found

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) 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. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000275300.3. 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
	SLC22A3	NM_021977.4	MANE Select	c.1510+845G>C		intron	N/A	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.1510+845G>C		intron	N/A	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42249 AN: 151734 Hom.: 6048 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.278 AC: 42284 AN: 151854 Hom.: 6055 Cov.: 31 AF XY: 0.281 AC XY: 20840 AN XY: 74226

African (AFR) AF: 0.239 AC: 9901 AN: 41406

American (AMR) AF: 0.219 AC: 3353 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2108 AN: 5126

South Asian (SAS) AF: 0.394 AC: 1888 AN: 4796

European-Finnish (FIN) AF: 0.295 AC: 3116 AN: 10554

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.289 AC: 19633 AN: 67906

Other (OTH) AF: 0.313 AC: 660 AN: 2112

Alfa AF: 0.283 Hom.: 758

Bravo AF: 0.272

Asia WGS AF: 0.397 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.39
PhyloP100		0.67
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: rs2457576; hg19: chr6-160865619;