rs36060036

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003361.4(UMOD):c.88+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,248 control chromosomes in the GnomAD database, including 20,422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1514 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18908 hom. )

Consequence

UMOD
NM_003361.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.458

Publications

9 publications found

Variant links:

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

UMOD links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003361.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 16-20350628-C-T is Benign according to our data. Variant chr16-20350628-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UMOD	NM_003361.4	MANE Select	c.88+22G>A	intron	N/A	NP_003352.2	P07911-1
UMOD	NM_001378234.1		c.88+22G>A	intron	N/A	NP_001365163.1
UMOD	NM_001378235.1		c.88+22G>A	intron	N/A	NP_001365164.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UMOD	ENST00000396138.9	TSL:5 MANE Select	c.88+22G>A	intron	N/A	ENSP00000379442.5	P07911-1
UMOD	ENST00000396134.6	TSL:2	c.88+22G>A	intron	N/A	ENSP00000379438.2	P07911-5
UMOD	ENST00000863077.1		c.88+22G>A	intron	N/A	ENSP00000533136.1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18745

AN:

152088

Hom.:

1514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0296

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.00540

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.129

GnomAD2 exomes

AF:

0.139

AC:

34711

AN:

249662

AF XY:

0.143

show subpopulations

Gnomad AFR exome

AF:

0.0243

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.00757

Gnomad FIN exome

AF:

0.218

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.156

AC:

228156

AN:

1461042

Hom.:

18908

Cov.:

AF XY:

0.156

AC XY:

113384

AN XY:

726788

show subpopulations

African (AFR)

AF:

0.0256

AC:

858

AN:

33452

American (AMR)

AF:

0.137

AC:

6116

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

3411

AN:

26118

East Asian (EAS)

AF:

0.00335

AC:

133

AN:

39692

South Asian (SAS)

AF:

0.140

AC:

12064

AN:

86166

European-Finnish (FIN)

AF:

0.219

AC:

11664

AN:

53356

Middle Eastern (MID)

AF:

0.142

AC:

821

AN:

5768

European-Non Finnish (NFE)

AF:

0.166

AC:

184347

AN:

1111472

Other (OTH)

AF:

0.145

AC:

8742

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10270

20540

30811

41081

51351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6438

12876

19314

25752

32190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.123

AC:

18734

AN:

152206

Hom.:

1514

Cov.:

AF XY:

0.126

AC XY:

9342

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0295

AC:

1226

AN:

41540

American (AMR)

AF:

0.154

AC:

2351

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

469

AN:

3472

East Asian (EAS)

AF:

0.00522

AC:

AN:

5176

South Asian (SAS)

AF:

0.126

AC:

608

AN:

4828

European-Finnish (FIN)

AF:

0.222

AC:

2348

AN:

10582

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11222

AN:

67996

Other (OTH)

AF:

0.128

AC:

270

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

836

1671

2507

3342

4178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.136

Hom.:

328

Bravo

AF:

0.113

Asia WGS

AF:

0.0710

AC:

248

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.82

(source)

DANN

Benign

0.46

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over