rs13333226

Variant names:

• chr16-20354332-A-G
• rs13333226
• ENST00000570689.5:c.-40+1862T>C

Variant summary

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

The ENST00000863071.1(UMOD):​c.-103+1862T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,980 control chromosomes in the GnomAD database, including 4,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.23 (4388 hom., cov: 32)
• Consequence: UMOD ENST00000863071.1 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.649
• Publications: 84 publications found

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]

UMOD Gene-Disease associations (from GenCC):

• autosomal dominant medullary cystic kidney disease with or without hyperuricemia

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• glomerulocystic kidney disease with hyperuricemia and isosthenuria

  Inheritance: AD Classification: DEFINITIVE Submitted by: Laboratory for Molecular Medicine
• familial juvenile hyperuricemic nephropathy type 1

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• autosomal dominant medullary cystic kidney disease with hyperuricemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000863071.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMOD	ENST00000570689.5	TSL:5	c.-40+1862T>C		intron	N/A	ENSP00000460548.1	P07911-1
	UMOD	ENST00000863071.1		c.-103+1862T>C		intron	N/A	ENSP00000533130.1
	UMOD	ENST00000863072.1		c.-40+1878T>C		intron	N/A	ENSP00000533131.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35047 AN: 151860 Hom.: 4377 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0737

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.231 AC: 35090 AN: 151980 Hom.: 4388 Cov.: 32 AF XY: 0.234 AC XY: 17361 AN XY: 74290

African (AFR) AF: 0.327 AC: 13537 AN: 41402

American (AMR) AF: 0.242 AC: 3694 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 512 AN: 3472

East Asian (EAS) AF: 0.0736 AC: 381 AN: 5174

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4820

European-Finnish (FIN) AF: 0.227 AC: 2404 AN: 10576

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12418 AN: 67958

Other (OTH) AF: 0.214 AC: 452 AN: 2112

Alfa AF: 0.193 Hom.: 10891

Bravo AF: 0.234

Asia WGS AF: 0.205 AC: 714 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Essential hypertension (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.88
DANN	Benign	0.60
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13333226; hg19: chr16-20365654;