rs2282142

Positions:

• chr6-160136483-G-A

Variant summary

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

The NM_003057.3(SLC22A1):​c.955-61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 1,543,926 control chromosomes in the GnomAD database, including 1,217 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 0.032 (139 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1078 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.955-61G>A		intron_variant		ENST00000366963.9
SLC22A1	NM_153187.2	c.955-61G>A		intron_variant
SLC22A1	XM_005267103.3	c.955-61G>A		intron_variant
SLC22A1	XM_006715552.3	c.955-61G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.955-61G>A		intron_variant		1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4839 AN: 152126 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.00792

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0245 AC: 34078 AN: 1391682 Hom.: 1078 Cov.: 24 AF XY: 0.0260 AC XY: 18066 AN XY: 696128

Gnomad4 AFR exome AF: 0.0503

Gnomad4 AMR exome AF: 0.0428

Gnomad4 ASJ exome AF: 0.000312

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.0728

Gnomad4 FIN exome AF: 0.00919

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0251

GnomAD4 genome AF: 0.0318 AC: 4847 AN: 152244 Hom.: 139 Cov.: 32 AF XY: 0.0343 AC XY: 2554 AN XY: 74432

Gnomad4 AFR AF: 0.0497

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.0834

Gnomad4 FIN AF: 0.00792

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0269 Hom.: 13

Bravo AF: 0.0332

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.66

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: rs2282142; hg19: chr6-160557515; COSMIC: COSV61452537; COSMIC: COSV61452537;