chr5-132301616-C-T

Variant names:

• chr5-132301616-C-T
• rs3792876
• NM_003059.3:c.393+6607C>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.393+6607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 152,254 control chromosomes in the GnomAD database, including 532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.072 (532 hom., cov: 33)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -1.40
• Publications: 26 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]

SLC22A4 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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 (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

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.393+6607C>T		intron	N/A	NP_003050.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.393+6607C>T		intron	N/A	ENSP00000200652.3	Q9H015
	SLC22A4	ENST00000947750.1		c.393+6607C>T		intron	N/A	ENSP00000617809.1
	SLC22A4	ENST00000897525.1		c.393+6607C>T		intron	N/A	ENSP00000567584.1

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10909 AN: 152136 Hom.: 535 Cov.: 33

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0716 AC: 10908 AN: 152254 Hom.: 532 Cov.: 33 AF XY: 0.0710 AC XY: 5286 AN XY: 74448

African (AFR) AF: 0.0449 AC: 1865 AN: 41544

American (AMR) AF: 0.0457 AC: 700 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 363 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1387 AN: 5166

South Asian (SAS) AF: 0.0648 AC: 313 AN: 4828

European-Finnish (FIN) AF: 0.0767 AC: 814 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0764 AC: 5199 AN: 68014

Other (OTH) AF: 0.0710 AC: 150 AN: 2114

Alfa AF: 0.0718 Hom.: 544

Bravo AF: 0.0685

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Rheumatoid arthritis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.56
PhyloP100		-1.4
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: rs3792876; hg19: chr5-131637309;