rs8177515

Variant names:

• chr6-160243648-G-A
• rs8177515
• NM_003058.4:c.1203C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-160243648-G-A
• chr6-160243648-G-C
• chr6-160243648-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003058.4(SLC22A2):​c.1203C>T​(p.Ile401Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,614,012 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (10 hom.)
• Consequence: SLC22A2 NM_003058.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.76
• Publications: 7 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-160243648-G-A is Benign according to our data. Variant chr6-160243648-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.76 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003058.4. 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
	SLC22A2	NM_003058.4	MANE Select	c.1203C>T	p.Ile401Ile	synonymous	Exon 7 of 11	NP_003049.2	O15244-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.1203C>T	p.Ile401Ile	synonymous	Exon 7 of 11	ENSP00000355920.3	O15244-1
	SLC22A2	ENST00000486916.5	TSL:3	n.242C>T		non_coding_transcript_exon	Exon 2 of 6
	SLC22A2	ENST00000491092.1	TSL:5	n.1100C>T		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 384 AN: 152092 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00441

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00274 AC: 689 AN: 251298 AF XY: 0.00290

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00466

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00440

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00326 AC: 4760 AN: 1461802 Hom.: 10 Cov.: 31 AF XY: 0.00329 AC XY: 2394 AN XY: 727214

African (AFR) AF: 0.000418 AC: 14 AN: 33476

American (AMR) AF: 0.00266 AC: 119 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00532 AC: 139 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000638 AC: 55 AN: 86256

European-Finnish (FIN) AF: 0.000955 AC: 51 AN: 53418

Middle Eastern (MID) AF: 0.00468 AC: 27 AN: 5766

European-Non Finnish (NFE) AF: 0.00377 AC: 4195 AN: 1111946

Other (OTH) AF: 0.00265 AC: 160 AN: 60390

GnomAD4 genome AF: 0.00252 AC: 384 AN: 152210 Hom.: 3 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74412

African (AFR) AF: 0.000650 AC: 27 AN: 41540

American (AMR) AF: 0.00190 AC: 29 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00441 AC: 300 AN: 68000

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00362 Hom.: 2

Bravo AF: 0.00237

EpiCase AF: 0.00545

EpiControl AF: 0.00522

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0050
DANN	Benign	0.52
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism

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: rs8177515; hg19: chr6-160664680; COSMIC: COSV65265922; COSMIC: COSV65265922;