6-160153005-C-T

Variant names:

• chr6-160153005-C-T
• rs4709402
• NM_003057.3:c.1386-1793C>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.1386-1793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,660 control chromosomes in the GnomAD database, including 10,486 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 0.37 (10486 hom., cov: 32)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1386-1793C>T		intron_variant	Intron 8 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1386-2970C>T		intron_variant	Intron 8 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.1386-5511C>T		intron_variant	Intron 8 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.1386-1793C>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.1386-1793C>T		intron_variant	Intron 8 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56028 AN: 151542 Hom.: 10487 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.370 AC: 56047 AN: 151660 Hom.: 10486 Cov.: 32 AF XY: 0.366 AC XY: 27145 AN XY: 74118

African (AFR) AF: 0.327 AC: 13526 AN: 41312

American (AMR) AF: 0.293 AC: 4471 AN: 15252

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

East Asian (EAS) AF: 0.328 AC: 1691 AN: 5158

South Asian (SAS) AF: 0.364 AC: 1755 AN: 4818

European-Finnish (FIN) AF: 0.362 AC: 3804 AN: 10510

Middle Eastern (MID) AF: 0.486 AC: 139 AN: 286

European-Non Finnish (NFE) AF: 0.404 AC: 27418 AN: 67854

Other (OTH) AF: 0.395 AC: 832 AN: 2104

Alfa AF: 0.389 Hom.: 1433

Bravo AF: 0.364

Asia WGS AF: 0.338 AC: 1173 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	3.3
DANN	Benign	0.46
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: rs4709402; hg19: chr6-160574037; COSMIC: COSV61452480; COSMIC: COSV61452480;