16-20356368-G-T

Variant names:

• chr16-20356368-G-T
• rs12917707
• ENST00000570689.5:c.-214C>A

Variant summary

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

The ENST00000570689.5(UMOD):​c.-214C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,638 control chromosomes in the GnomAD database, including 1,791 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 0.14 (1788 hom., cov: 32)
  • Exomes 𝑓: 0.081 (3 hom.)
• Consequence: UMOD ENST00000570689.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMOD	XM_011545938.1	c.-214C>A		upstream_gene_variant			XP_011544240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMOD	ENST00000570689.5	c.-214C>A		upstream_gene_variant		5		ENSP00000460548.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20935 AN: 152114 Hom.: 1786 Cov.: 32

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0813 AC: 33 AN: 406 Hom.: 3 AF XY: 0.0940 AC XY: 22 AN XY: 234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.0865

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.138 AC: 20937 AN: 152232 Hom.: 1788 Cov.: 32 AF XY: 0.139 AC XY: 10341 AN XY: 74428

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.151

Alfa AF: 0.157 Hom.: 2464

Bravo AF: 0.129

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12917707; hg19: chr16-20367690;