rs4646275

Positions:

• chr6-160131975-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.516-257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,164 control chromosomes in the GnomAD database, including 1,758 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 0.13 (1758 hom., cov: 32)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.516-257C>T		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.516-257C>T		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.516-257C>T		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.516-257C>T		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.516-257C>T		intron_variant		1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19637 AN: 152046 Hom.: 1756 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.129 AC: 19658 AN: 152164 Hom.: 1758 Cov.: 32 AF XY: 0.130 AC XY: 9654 AN XY: 74382

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0646

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0945 Hom.: 1665

Bravo AF: 0.147

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.39
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4646275; hg19: chr6-160553007;