chr6-160247357-A-G

Position:

• chr6-160247357-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003058.4(SLC22A2):​c.843-59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 871,950 control chromosomes in the GnomAD database, including 7,137 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 0.14 (1543 hom., cov: 33)
  • Exomes 𝑓: 0.12 (5594 hom.)
• Consequence: SLC22A2 NM_003058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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]

SLC22A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A2	NM_003058.4	c.843-59T>C		intron_variant		ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366953.8	c.843-59T>C		intron_variant		1	NM_003058.4	ENSP00000355920.3
SLC22A2	ENST00000366952.1	c.780-59T>C		intron_variant		5		ENSP00000355919.1
SLC22A2	ENST00000491092.1	n.740-59T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20592 AN: 152072 Hom.: 1531 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.0819

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.117 AC: 84501 AN: 719760 Hom.: 5594 AF XY: 0.115 AC XY: 44468 AN XY: 385404

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0583

Gnomad4 ASJ exome AF: 0.0671

Gnomad4 EAS exome AF: 0.0751

Gnomad4 SAS exome AF: 0.0855

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.136 AC: 20640 AN: 152190 Hom.: 1543 Cov.: 33 AF XY: 0.131 AC XY: 9770 AN XY: 74414

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0878

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.0907

Gnomad4 SAS AF: 0.0822

Gnomad4 FIN AF: 0.0949

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.120

Alfa AF: 0.120 Hom.: 2289

Bravo AF: 0.137

Asia WGS AF: 0.0850 AC: 294 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	0.93
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2279463; hg19: chr6-160668389; COSMIC: COSV65265716; COSMIC: COSV65265716;