rs4709401

Variant names:

• chr6-160152995-C-T
• rs4709401
• NM_003057.3:c.1386-1803C>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.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
• Publications: 7 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=-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 rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1386-1803C>T		intron_variant	Intron 8 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1386-2980C>T		intron_variant	Intron 8 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.1386-5521C>T		intron_variant	Intron 8 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.1386-1803C>T		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.1386-1803C>T		intron_variant	Intron 8 of 10	1	NM_003057.3	ENSP00000355930.4

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

African (AFR) AF: 0.602 AC: 24864 AN: 41278

American (AMR) AF: 0.317 AC: 4824 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1845 AN: 3462

East Asian (EAS) AF: 0.327 AC: 1691 AN: 5166

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4812

European-Finnish (FIN) AF: 0.362 AC: 3801 AN: 10508

Middle Eastern (MID) AF: 0.528 AC: 152 AN: 288

European-Non Finnish (NFE) AF: 0.405 AC: 27496 AN: 67856

Other (OTH) AF: 0.453 AC: 954 AN: 2104

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
PhyloP100		0.12
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: rs4709401; hg19: chr6-160574027; COSMIC: COSV61452476; COSMIC: COSV61452476;