rs1050152

Positions:

• chr5-132340627-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003059.3(SLC22A4):​c.1507C>T​(p.Leu503Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,612,884 control chromosomes in the GnomAD database, including 122,654 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7827 hom., cov: 31)
  • Exomes 𝑓: 0.38 (114827 hom.)
• Consequence: SLC22A4 NM_003059.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.226

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) 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. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015764236).
• BP6: Variant 5-132340627-C-T is Benign according to our data. Variant chr5-132340627-C-T is described in ClinVar as [Benign]. Clinvar id is 5750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.1507C>T	p.Leu503Phe	missense_variant	9/10	ENST00000200652.4	NP_003050.2
MIR3936HG	NR_110997.1	n.561-5701G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.1507C>T	p.Leu503Phe	missense_variant	9/10	1	NM_003059.3	ENSP00000200652	P1
MIR3936HG	ENST00000621103.4	n.561-5701G>A		intron_variant, non_coding_transcript_variant		1
MIR3936HG	ENST00000616965.1	n.344-5701G>A		intron_variant, non_coding_transcript_variant		5
MIR3936HG	ENST00000669845.1	n.187-5701G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42572 AN: 151868 Hom.: 7830 Cov.: 31

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.326

GnomAD3 exomes AF: 0.294 AC: 73900 AN: 251468 Hom.: 13886 AF XY: 0.297 AC XY: 40314 AN XY: 135912

Gnomad AFR exome AF: 0.0722

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.00120

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.427

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.378 AC: 551801 AN: 1460898 Hom.: 114827 Cov.: 34 AF XY: 0.372 AC XY: 270348 AN XY: 726798

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.280 AC: 42559 AN: 151986 Hom.: 7827 Cov.: 31 AF XY: 0.269 AC XY: 20004 AN XY: 74272

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.00252

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.321

Alfa AF: 0.387 Hom.: 24299

Bravo AF: 0.275

TwinsUK AF: 0.435 AC: 1612

ALSPAC AF: 0.437 AC: 1683

ESP6500AA AF: 0.0833 AC: 367

ESP6500EA AF: 0.419 AC: 3607

ExAC AF: 0.291 AC: 35363

Asia WGS AF: 0.0560 AC: 195 AN: 3478

EpiCase AF: 0.428

EpiControl AF: 0.434

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 23127916, 30643255, 15107849, 17700366, 21816865, 22325173, 21793125, 21279723, 22206629) -

SLC22A4 POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Oct 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.99	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Benign	0.10	T
Sift4G	Benign	0.12	T
Polyphen		0.0060	B
Vest4		0.036
MPC		0.30
ClinPred		0.0054	T
GERP RS		-4.6
Varity_R		0.14
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1050152; hg19: chr5-131676320; COSMIC: COSV52357336;