6-160146347-A-G

Variant names:

• chr6-160146347-A-G
• rs637841
• NM_003057.3:c.1385+2698A>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.1385+2698A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,940 control chromosomes in the GnomAD database, including 14,592 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 0.44 (14592 hom., cov: 32)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• 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]

ENSG00000301636 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1385+2698A>G		intron_variant	Intron 8 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1385+2698A>G		intron_variant	Intron 8 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.1385+2698A>G		intron_variant	Intron 8 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.1385+2698A>G		intron_variant	Intron 8 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1385+2698A>G		intron_variant	Intron 8 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66286 AN: 151822 Hom.: 14575 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.437 AC: 66342 AN: 151940 Hom.: 14592 Cov.: 32 AF XY: 0.436 AC XY: 32384 AN XY: 74252

African (AFR) AF: 0.442 AC: 18284 AN: 41388

American (AMR) AF: 0.483 AC: 7384 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1914 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1804 AN: 5174

South Asian (SAS) AF: 0.452 AC: 2172 AN: 4806

European-Finnish (FIN) AF: 0.360 AC: 3787 AN: 10520

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29350 AN: 67976

Other (OTH) AF: 0.464 AC: 980 AN: 2114

Alfa AF: 0.434 Hom.: 1801

Bravo AF: 0.446

Asia WGS AF: 0.384 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.39
DANN	Benign	0.54
PhyloP100		-3.0
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: rs637841; hg19: chr6-160567379;