rs3798174

Variant names:

• chr6-160131771-C-T
• rs3798174
• NM_003057.3:c.516-461C>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.516-461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 152,074 control chromosomes in the GnomAD database, including 479 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 0.074 (479 hom., cov: 32)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 16 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.516-461C>T		intron_variant	Intron 2 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.516-461C>T		intron_variant	Intron 2 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.516-461C>T		intron_variant	Intron 2 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.516-461C>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.516-461C>T		intron_variant	Intron 2 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11299 AN: 151958 Hom.: 480 Cov.: 32

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0840

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

GnomAD4 genome AF: 0.0743 AC: 11303 AN: 152074 Hom.: 479 Cov.: 32 AF XY: 0.0727 AC XY: 5404 AN XY: 74336

African (AFR) AF: 0.0922 AC: 3821 AN: 41460

American (AMR) AF: 0.0729 AC: 1114 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5184

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4820

European-Finnish (FIN) AF: 0.0532 AC: 564 AN: 10592

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0694 AC: 4715 AN: 67960

Other (OTH) AF: 0.0850 AC: 179 AN: 2106

Alfa AF: 0.0732 Hom.: 874

Bravo AF: 0.0763

Asia WGS AF: 0.0590 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.079
DANN	Benign	0.59
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3798174; hg19: chr6-160552803;