rs4709401

Positions:

• chr6-160152995-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003057.3(SLC22A1):​c.1386-1803C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,618 control chromosomes in the GnomAD database, including 16,013 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 0.45 (16013 hom., cov: 31)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.1386-1803C>T		intron_variant		ENST00000366963.9
SLC22A1	NM_153187.2	c.1386-2980C>T		intron_variant
SLC22A1	XM_005267103.3	c.1386-1803C>T		intron_variant
SLC22A1	XM_006715552.3	c.1386-5521C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1386-1803C>T		intron_variant		1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67897 AN: 151500 Hom.: 15994 Cov.: 31

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.448 AC: 67959 AN: 151618 Hom.: 16013 Cov.: 31 AF XY: 0.441 AC XY: 32671 AN XY: 74092

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.453

Alfa AF: 0.433 Hom.: 1812

Bravo AF: 0.455

Asia WGS AF: 0.358 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs4709401; hg19: chr6-160574027; COSMIC: COSV61452476; COSMIC: COSV61452476;