rs41267797

Variant names:

• chr6-160155979-G-A
• rs41267797
• NM_003057.3:c.1503G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160155979-G-A
• chr6-160155979-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153187.2(SLC22A1):​c.1390G>A​(p.Val464Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,613,858 control chromosomes in the GnomAD database, including 1,244 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.059 (538 hom., cov: 32)
  • Exomes 𝑓: 0.020 (706 hom.)
• Consequence: SLC22A1 NM_153187.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606
• Publications: 17 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 (MetaRNN=0.0036869347).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153187.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	NM_003057.3	MANE Select	c.1503G>A	p.Val501Val	synonymous	Exon 10 of 11	NP_003048.1
	SLC22A1	NM_153187.2		c.1390G>A	p.Val464Ile	missense	Exon 9 of 10	NP_694857.1
	SLC22A1	NM_001437335.1		c.1386-2537G>A		intron	N/A	NP_001424264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.1503G>A	p.Val501Val	synonymous	Exon 10 of 11	ENSP00000355930.4
	SLC22A1	ENST00000324965.8	TSL:5	c.1390G>A	p.Val464Ile	missense	Exon 9 of 10	ENSP00000318103.4
	SLC22A1	ENST00000898298.1		c.1617G>A	p.Val539Val	synonymous	Exon 11 of 12	ENSP00000568357.1

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8928 AN: 152032 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0266

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0499

GnomAD2 exomes AF: 0.0292 AC: 7337 AN: 251384 AF XY: 0.0264

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.0335

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.000816

Gnomad FIN exome AF: 0.0301

Gnomad NFE exome AF: 0.0167

Gnomad OTH exome AF: 0.0223

GnomAD4 exome AF: 0.0204 AC: 29778 AN: 1461708 Hom.: 706 Cov.: 30 AF XY: 0.0199 AC XY: 14488 AN XY: 727168

African (AFR) AF: 0.169 AC: 5643 AN: 33444

American (AMR) AF: 0.0323 AC: 1444 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 291 AN: 26132

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39700

South Asian (SAS) AF: 0.0193 AC: 1665 AN: 86250

European-Finnish (FIN) AF: 0.0295 AC: 1577 AN: 53402

Middle Eastern (MID) AF: 0.0338 AC: 195 AN: 5768

European-Non Finnish (NFE) AF: 0.0156 AC: 17304 AN: 1111914

Other (OTH) AF: 0.0271 AC: 1634 AN: 60380

GnomAD4 genome AF: 0.0589 AC: 8960 AN: 152150 Hom.: 538 Cov.: 32 AF XY: 0.0574 AC XY: 4270 AN XY: 74386

African (AFR) AF: 0.163 AC: 6740 AN: 41460

American (AMR) AF: 0.0319 AC: 488 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3468

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5170

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4822

European-Finnish (FIN) AF: 0.0266 AC: 282 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0171 AC: 1165 AN: 68016

Other (OTH) AF: 0.0494 AC: 104 AN: 2106

Alfa AF: 0.0268 Hom.: 646

Bravo AF: 0.0634

TwinsUK AF: 0.0170 AC: 63

ALSPAC AF: 0.0140 AC: 54

ESP6500AA AF: 0.150 AC: 659

ESP6500EA AF: 0.0170 AC: 146

ExAC AF: 0.0316 AC: 3839

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0158

EpiControl AF: 0.0158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.19
DANN	Benign	0.83
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.61
PROVEAN	Benign	0.76	N
REVEL	Benign	0.063
Sift	Benign	0.24	T
Sift4G	Benign	0.23	T
Polyphen		0.0030	B
Vest4		0.17
ClinPred		0.0017	T
GERP RS		-4.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs41267797; hg19: chr6-160577011; COSMIC: COSV108138562;