rs4646276

Positions:

• chr6-160136122-G-A
• chr6-160136122-G-C

Variant summary

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

The NM_003057.3(SLC22A1):​c.840-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 901,180 control chromosomes in the GnomAD database, including 9,573 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 0.12 (1608 hom., cov: 32)
  • Exomes 𝑓: 0.12 (7965 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.840-98G>A		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.840-98G>A		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.840-98G>A		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.840-98G>A		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.840-98G>A		intron_variant		1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18744 AN: 152096 Hom.: 1606 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.117 AC: 87356 AN: 748966 Hom.: 7965 AF XY: 0.116 AC XY: 45385 AN XY: 390522

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.0876

Gnomad4 EAS exome AF: 0.421

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0700

Gnomad4 NFE exome AF: 0.0822

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.123 AC: 18766 AN: 152214 Hom.: 1608 Cov.: 32 AF XY: 0.124 AC XY: 9261 AN XY: 74430

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0646

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0620 Hom.: 92

Bravo AF: 0.140

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.47

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: rs4646276; hg19: chr6-160557154; COSMIC: COSV61453788; COSMIC: COSV61453788;