chr5-132312232-C-T

Variant names:

• chr5-132312232-C-T
• rs11568511
• NM_003059.3:c.465C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_003059.3(SLC22A4):​c.465C>T​(p.Leu155Leu) 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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003059.3. 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
	SLC22A4	NM_003059.3	MANE Select	c.465C>T	p.Leu155Leu	synonymous	Exon 2 of 10	NP_003050.2
	MIR3936HG	NR_110997.1		n.846G>A		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.465C>T	p.Leu155Leu	synonymous	Exon 2 of 10	ENSP00000200652.3	Q9H015
	MIR3936HG	ENST00000621103.4	TSL:1	n.846G>A		non_coding_transcript_exon	Exon 8 of 8
	SLC22A4	ENST00000947750.1		c.465C>T	p.Leu155Leu	synonymous	Exon 2 of 10	ENSP00000617809.1

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

GnomAD2 exomes AF: 0.00413 AC: 1039 AN: 251446 AF XY: 0.00496

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 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

African (AFR) AF: 0.000657 AC: 22 AN: 33468

American (AMR) AF: 0.00195 AC: 87 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00371 AC: 97 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0197 AC: 1696 AN: 86250

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.00971 AC: 56 AN: 5768

European-Non Finnish (NFE) AF: 0.00191 AC: 2119 AN: 1111440

Other (OTH) AF: 0.00399 AC: 241 AN: 60364

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

African (AFR) AF: 0.000241 AC: 10 AN: 41552

American (AMR) AF: 0.00144 AC: 22 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0188 AC: 91 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00265 AC: 180 AN: 68006

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	SLC22A4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.030
DANN	Benign	0.76
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism

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: rs11568511; hg19: chr5-131647925;