rs4646274

chr6-160131004-C-Gchr6-160131004-C-T

Variant summary

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

The NM_003057.3(SLC22A1):c.515+797C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 151,932 control chromosomes in the GnomAD database, including 765 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 0.067 (765 hom., cov: 31)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

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 = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.515+797C>G		intron_variant		ENST00000366963.9
SLC22A1	NM_153187.2	c.515+797C>G		intron_variant
SLC22A1	XM_005267103.3	c.515+797C>G		intron_variant
SLC22A1	XM_006715552.3	c.515+797C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.515+797C>G		intron_variant		1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10148 AN: 151814 Hom.: 764 Cov.: 31

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0384

Gnomad OTH AF: 0.0605

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

GnomAD4 genome AF: 0.0669 AC: 10157 AN: 151932 Hom.: 765 Cov.: 31 AF XY: 0.0687 AC XY: 5098 AN XY: 74258

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.0862

Gnomad4 FIN AF: 0.0426

Gnomad4 NFE AF: 0.0384

Gnomad4 OTH AF: 0.0651

Alfa AF: 0.0217 Hom.: 10

Bravo AF: 0.0788

Asia WGS AF: 0.230 AC: 801 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	4.6
Dann	Benign	0.67

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: rs4646274; hg19: chr6-160552036;