rs270608

Variant names:

• chr5-132312713-C-T
• rs270608
• NM_003059.3:c.497+449C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003059.3(SLC22A4):​c.497+449C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,166 control chromosomes in the GnomAD database, including 39,404 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 0.71 (39404 hom., cov: 33)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.497+449C>T		intron_variant	Intron 2 of 9	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.497+449C>T		intron_variant	Intron 2 of 9	1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.825-460G>A		intron_variant	Intron 7 of 7	1
SLC22A4	ENST00000491257.1	n.301+449C>T		intron_variant	Intron 2 of 3	4
MIR3936HG	ENST00000669845.1	n.451-460G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108236 AN: 152048 Hom.: 39353 Cov.: 33

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.713

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.712 AC: 108343 AN: 152166 Hom.: 39404 Cov.: 33 AF XY: 0.700 AC XY: 52026 AN XY: 74372

African (AFR) AF: 0.847 AC: 35189 AN: 41542

American (AMR) AF: 0.707 AC: 10821 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2346 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3193 AN: 5170

South Asian (SAS) AF: 0.433 AC: 2086 AN: 4822

European-Finnish (FIN) AF: 0.553 AC: 5858 AN: 10586

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46381 AN: 67960

Other (OTH) AF: 0.713 AC: 1505 AN: 2112

Alfa AF: 0.692 Hom.: 4570

Bravo AF: 0.737

Asia WGS AF: 0.528 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.055
DANN	Benign	0.20
PhyloP100		-0.29
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: rs270608; hg19: chr5-131648406;