rs4646273

Positions:

• chr6-160130304-G-A
• chr6-160130304-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.515+97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 931,312 control chromosomes in the GnomAD database, including 5,512 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 0.054 (699 hom., cov: 31)
  • Exomes 𝑓: 0.067 (4813 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.404

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=-0.9).
• 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	Protein	UniProt
SLC22A1	NM_003057.3	c.515+97G>A		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.515+97G>A		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.515+97G>A		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.515+97G>A		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.515+97G>A		intron_variant		1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8181 AN: 152010 Hom.: 698 Cov.: 31

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.0858

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0547

GnomAD4 exome AF: 0.0668 AC: 52040 AN: 779184 Hom.: 4813 AF XY: 0.0650 AC XY: 26710 AN XY: 410764

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.00824

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.0834

Gnomad4 FIN exome AF: 0.0449

Gnomad4 NFE exome AF: 0.0368

Gnomad4 OTH exome AF: 0.0568

GnomAD4 genome AF: 0.0538 AC: 8186 AN: 152128 Hom.: 699 Cov.: 31 AF XY: 0.0565 AC XY: 4205 AN XY: 74400

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.0861

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0382

Gnomad4 OTH AF: 0.0594

Alfa AF: 0.0398 Hom.: 264

Bravo AF: 0.0640

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.56

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: rs4646273; hg19: chr6-160551336; COSMIC: COSV104412180;