rs4238595

Variant names:

• chr16-20331769-T-C
• rs4238595
• ENST00000863076.1:c.*1545A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-20331769-T-C
• chr16-20331769-T-G

Variant summary

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

The ENST00000863076.1(UMOD):​c.*1545A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.775 in 152,208 control chromosomes in the GnomAD database, including 46,951 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 0.78 (46951 hom., cov: 33)
• Consequence: UMOD ENST00000863076.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000863076.1. 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	ENST00000863076.1		c.*1545A>G		3_prime_UTR	Exon 12 of 12	ENSP00000533135.1

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117897 AN: 152090 Hom.: 46891 Cov.: 33

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.775 AC: 118011 AN: 152208 Hom.: 46951 Cov.: 33 AF XY: 0.773 AC XY: 57521 AN XY: 74402

African (AFR) AF: 0.943 AC: 39209 AN: 41562

American (AMR) AF: 0.685 AC: 10481 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2644 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5142 AN: 5182

South Asian (SAS) AF: 0.849 AC: 4094 AN: 4820

European-Finnish (FIN) AF: 0.675 AC: 7138 AN: 10580

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46884 AN: 67986

Other (OTH) AF: 0.766 AC: 1618 AN: 2112

Alfa AF: 0.711 Hom.: 75324

Bravo AF: 0.784

Asia WGS AF: 0.914 AC: 3181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.31
DANN	Benign	0.79
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs4238595; hg19: chr16-20343091;