rs4646275

Variant names:

• chr6-160131975-C-T
• rs4646275
• NM_003057.3:c.516-257C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.516-257C>T		intron_variant	Intron 2 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.516-257C>T		intron_variant	Intron 2 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.516-257C>T		intron_variant	Intron 2 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.516-257C>T		intron_variant	Intron 2 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.516-257C>T		intron_variant	Intron 2 of 10	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

African (AFR) AF: 0.158 AC: 6561 AN: 41520

American (AMR) AF: 0.216 AC: 3292 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2112 AN: 5142

South Asian (SAS) AF: 0.156 AC: 753 AN: 4818

European-Finnish (FIN) AF: 0.0646 AC: 686 AN: 10612

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0822 AC: 5588 AN: 68006

Other (OTH) AF: 0.139 AC: 295 AN: 2116

Alfa AF: 0.101 Hom.: 2698

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4646275; hg19: chr6-160553007;