rs654993

Variant names:

• chr6-160147864-T-C
• rs654993
• NM_003057.3:c.1385+4215T>C

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+4215T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 151,970 control chromosomes in the GnomAD database, including 26,782 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 0.59 (26782 hom., cov: 32)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 10 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1385+4215T>C		intron_variant	Intron 8 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1385+4215T>C		intron_variant	Intron 8 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.1385+4215T>C		intron_variant	Intron 8 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.1385+4215T>C		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+4215T>C		intron_variant	Intron 8 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89816 AN: 151852 Hom.: 26729 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.592 AC: 89933 AN: 151970 Hom.: 26782 Cov.: 32 AF XY: 0.596 AC XY: 44301 AN XY: 74274

African (AFR) AF: 0.627 AC: 25974 AN: 41424

American (AMR) AF: 0.675 AC: 10314 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2634 AN: 5158

South Asian (SAS) AF: 0.621 AC: 2989 AN: 4814

European-Finnish (FIN) AF: 0.652 AC: 6882 AN: 10558

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37761 AN: 67954

Other (OTH) AF: 0.587 AC: 1238 AN: 2108

Alfa AF: 0.570 Hom.: 48971

Bravo AF: 0.597

Asia WGS AF: 0.597 AC: 2079 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	0.38
DANN	Benign	0.38
PhyloP100		-1.7
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: rs654993; hg19: chr6-160568896;