6-160135165-T-G

Variant names:

• chr6-160135165-T-G
• rs3798169
• NM_003057.3:c.839+1040T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003057.3(SLC22A1):​c.839+1040T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 152,270 control chromosomes in the GnomAD database, including 701 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 (701 hom., cov: 32)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	NM_003057.3	MANE Select	c.839+1040T>G		intron	N/A	NP_003048.1
	SLC22A1	NM_153187.2		c.839+1040T>G		intron	N/A	NP_694857.1
	SLC22A1	NM_001437335.1		c.839+1040T>G		intron	N/A	NP_001424264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.839+1040T>G		intron	N/A	ENSP00000355930.4
	SLC22A1	ENST00000324965.8	TSL:5	c.839+1040T>G		intron	N/A	ENSP00000318103.4
	SLC22A1	ENST00000457470.6	TSL:5	c.839+1040T>G		intron	N/A	ENSP00000409557.2

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 8206 AN: 152152 Hom.: 700 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0546

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

GnomAD4 genome AF: 0.0539 AC: 8211 AN: 152270 Hom.: 701 Cov.: 32 AF XY: 0.0567 AC XY: 4222 AN XY: 74472

African (AFR) AF: 0.0101 AC: 421 AN: 41550

American (AMR) AF: 0.144 AC: 2204 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1951 AN: 5174

South Asian (SAS) AF: 0.0873 AC: 422 AN: 4832

European-Finnish (FIN) AF: 0.0425 AC: 451 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0383 AC: 2605 AN: 68020

Other (OTH) AF: 0.0593 AC: 125 AN: 2108

Alfa AF: 0.0420 Hom.: 418

Bravo AF: 0.0641

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.46
DANN	Benign	0.66
PhyloP100		-0.39
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: rs3798169; hg19: chr6-160556197;