rs41267797

chr6-160155979-G-Achr6-160155979-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003057.3(SLC22A1):c.1503G>A(p.Val501=) variant causes a synonymous 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. 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_003057.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036869347).
• BP7: Synonymous conserved (PhyloP=-0.606 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.1503G>A	p.Val501=	synonymous_variant	10/11	ENST00000366963.9
SLC22A1	NM_153187.2	c.1390G>A	p.Val464Ile	missense_variant	9/10
SLC22A1	XM_005267103.3	c.1591G>A	p.Val531Ile	missense_variant	11/12
SLC22A1	XM_006715552.3	c.1386-2537G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1503G>A	p.Val501=	synonymous_variant	10/11	1	NM_003057.3	P1

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

GnomAD3 exomes AF: 0.0292 AC: 7337 AN: 251384 Hom.: 286 AF XY: 0.0264 AC XY: 3591 AN XY: 135856

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 SAS exome AF: 0.0191

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

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.0323

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.000630

Gnomad4 SAS exome AF: 0.0193

Gnomad4 FIN exome AF: 0.0295

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0271

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

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0319

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0266

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0494

Alfa AF: 0.0238 Hom.: 246

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 v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	1.0	P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs41267797; hg19: chr6-160577011;