rs3798175

Variant names:

• chr6-160131545-G-T
• rs3798175
• NM_003057.3:c.516-687G>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.516-687G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 151,128 control chromosomes in the GnomAD database, including 186 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 0.038 (186 hom., cov: 28)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.516-687G>T		intron_variant	Intron 2 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.516-687G>T		intron_variant	Intron 2 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.516-687G>T		intron_variant	Intron 2 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.516-687G>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.516-687G>T		intron_variant	Intron 2 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5693 AN: 151020 Hom.: 186 Cov.: 28

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.00767

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0250

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

GnomAD4 genome AF: 0.0377 AC: 5701 AN: 151128 Hom.: 186 Cov.: 28 AF XY: 0.0401 AC XY: 2957 AN XY: 73786

African (AFR) AF: 0.0710 AC: 2919 AN: 41124

American (AMR) AF: 0.0376 AC: 569 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3460

East Asian (EAS) AF: 0.128 AC: 650 AN: 5094

South Asian (SAS) AF: 0.0843 AC: 401 AN: 4756

European-Finnish (FIN) AF: 0.00767 AC: 80 AN: 10430

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0149 AC: 1009 AN: 67830

Other (OTH) AF: 0.0248 AC: 52 AN: 2098

Alfa AF: 0.0282 Hom.: 14

Bravo AF: 0.0398

Asia WGS AF: 0.0920 AC: 318 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.5
DANN	Benign	0.82
PhyloP100		-0.23
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: rs3798175; hg19: chr6-160552577;