chr5-132312232-C-T

Position:

• chr5-132312232-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003059.3(SLC22A4):​c.465C>T​(p.Leu155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,613,532 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (28 hom.)
• Consequence: SLC22A4 NM_003059.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.41

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132312232-C-T is Benign according to our data. Variant chr5-132312232-C-T is described in ClinVar as [Benign]. Clinvar id is 785802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.41 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00207 (315/152270) while in subpopulation SAS AF= 0.0188 (91/4832). AF 95% confidence interval is 0.0157. There are 2 homozygotes in gnomad4. There are 165 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A4	NM_003059.3	c.465C>T	p.Leu155=	synonymous_variant	2/10	ENST00000200652.4
MIR3936HG	NR_110997.1	n.846G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A4	ENST00000200652.4	c.465C>T	p.Leu155=	synonymous_variant	2/10	1	NM_003059.3	P1
MIR3936HG	ENST00000621103.4	n.846G>A		non_coding_transcript_exon_variant	8/8	1
SLC22A4	ENST00000491257.1	n.269C>T		non_coding_transcript_exon_variant	2/4	4
MIR3936HG	ENST00000669845.1	n.472G>A		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 314 AN: 152152 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00265

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00413 AC: 1039 AN: 251446 Hom.: 7 AF XY: 0.00496 AC XY: 674 AN XY: 135898

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00476

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0195

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00263

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00296 AC: 4322 AN: 1461262 Hom.: 28 Cov.: 30 AF XY: 0.00357 AC XY: 2593 AN XY: 726960

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.00371

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0197

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.00399

GnomAD4 genome AF: 0.00207 AC: 315 AN: 152270 Hom.: 2 Cov.: 33 AF XY: 0.00222 AC XY: 165 AN XY: 74454

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0188

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00265

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00168

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.00365

EpiControl AF: 0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SLC22A4-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Dec 05, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.030
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs11568511; hg19: chr5-131647925;