rs13329952

chr16-20355185-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000570689.5(UMOD):c.-40+1009A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,926 control chromosomes in the GnomAD database, including 4,680 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 0.24 (4680 hom., cov: 31)
• Consequence: UMOD ENST00000570689.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

Genes affected

UMOD (HGNC:12559): (uromodulin) The protein encoded by this gene is the most abundant protein in mammalian urine under physiological conditions. Its excretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. This protein may act as a constitutive inhibitor of calcium crystallization in renal fluids. Excretion of this protein in urine may provide defense against urinary tract infections caused by uropathogenic bacteria. Defects in this gene are associated with the renal disorders medullary cystic kidney disease-2 (MCKD2), glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI), and familial juvenile hyperuricemic nephropathy (FJHN). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMOD	XM_011545938.1	c.-40+1009A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMOD	ENST00000570689.5	c.-40+1009A>G		intron_variant		5		P2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36377 AN: 151808 Hom.: 4673 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.240 AC: 36405 AN: 151926 Hom.: 4680 Cov.: 31 AF XY: 0.242 AC XY: 17998 AN XY: 74220

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.0733

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.229

Alfa AF: 0.219 Hom.: 537

Bravo AF: 0.242

Asia WGS AF: 0.206 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.7
Dann	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13329952; hg19: chr16-20366507;