chr5-132331660-A-G

Variant names:

• chr5-132331660-A-G
• rs273909
• NM_003059.3:c.952-96A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003059.3(SLC22A4):​c.952-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 847,052 control chromosomes in the GnomAD database, including 6,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (956 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5681 hom.)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50
• Publications: 84 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132331660-A-G is Benign according to our data. Variant chr5-132331660-A-G is described in ClinVar as Benign. ClinVar VariationId is 1248012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.952-96A>G		intron_variant	Intron 5 of 9	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.952-96A>G		intron_variant	Intron 5 of 9	1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.824+529T>C		intron_variant	Intron 7 of 7	1
MIR3936HG	ENST00000669845.1	n.450+529T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0957 AC: 14555 AN: 152126 Hom.: 956 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0842

GnomAD4 exome AF: 0.117 AC: 81408 AN: 694808 Hom.: 5681 AF XY: 0.121 AC XY: 45118 AN XY: 374156

African (AFR) AF: 0.0267 AC: 506 AN: 18956

American (AMR) AF: 0.0954 AC: 4161 AN: 43626

Ashkenazi Jewish (ASJ) AF: 0.0598 AC: 1275 AN: 21332

East Asian (EAS) AF: 0.0229 AC: 827 AN: 36182

South Asian (SAS) AF: 0.186 AC: 13144 AN: 70684

European-Finnish (FIN) AF: 0.207 AC: 10822 AN: 52228

Middle Eastern (MID) AF: 0.116 AC: 495 AN: 4272

European-Non Finnish (NFE) AF: 0.113 AC: 46417 AN: 412338

Other (OTH) AF: 0.107 AC: 3761 AN: 35190

GnomAD4 genome AF: 0.0956 AC: 14550 AN: 152244 Hom.: 956 Cov.: 32 AF XY: 0.101 AC XY: 7538 AN XY: 74440

African (AFR) AF: 0.0261 AC: 1085 AN: 41554

American (AMR) AF: 0.110 AC: 1678 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3472

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5180

South Asian (SAS) AF: 0.188 AC: 908 AN: 4824

European-Finnish (FIN) AF: 0.218 AC: 2313 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7926 AN: 68004

Other (OTH) AF: 0.0833 AC: 176 AN: 2112

Alfa AF: 0.105 Hom.: 3562

Bravo AF: 0.0800

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.73
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs273909; hg19: chr5-131667353; COSMIC: COSV52360930; COSMIC: COSV52360930;