NM_003361.4:c.1182+50C>T

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.1182+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,568,894 control chromosomes in the GnomAD database, including 274,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 19790 hom., cov: 33)

Exomes 𝑓: 0.58 ( 255035 hom. )

Consequence

UMOD
NM_003361.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.336

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: AD, Unknown 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

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=-0.77).

BP6

Variant 16-20346076-G-A is Benign according to our data. Variant chr16-20346076-G-A is described in ClinVar as Benign. ClinVar VariationId is 1279719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMOD	NM_003361.4 link	c.1182+50C>T		intron_variant	Intron 5 of 10	ENST00000396138.9	NP_003352.2	P07911-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UMOD	ENST00000396138.9 link	c.1182+50C>T	intron_variant	Intron 5 of 10	5	NM_003361.4	ENSP00000379442.5	P07911-1X6RBG4
UMOD	ENST00000396134.6 link	c.1281+50C>T	intron_variant	Intron 6 of 11	2		ENSP00000379438.2	P07911-5
UMOD	ENST00000570689.5 link	c.1182+50C>T	intron_variant	Intron 5 of 10	5		ENSP00000460548.1	P07911-1

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72404

AN:

151976

Hom.:

19788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.0785

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.498

GnomAD2 exomes

AF:

0.480

AC:

116820

AN:

243604

AF XY:

0.490

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.0801

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.636

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.583

AC:

826411

AN:

1416802

Hom.:

255035

Cov.:

AF XY:

0.578

AC XY:

407123

AN XY:

703946

show subpopulations

African (AFR)

AF:

0.251

AC:

8147

AN:

32516

American (AMR)

AF:

0.313

AC:

13792

AN:

44120

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

15398

AN:

25708

East Asian (EAS)

AF:

0.0580

AC:

2275

AN:

39230

South Asian (SAS)

AF:

0.357

AC:

30330

AN:

84952

European-Finnish (FIN)

AF:

0.589

AC:

31051

AN:

52744

Middle Eastern (MID)

AF:

0.509

AC:

2193

AN:

4312

European-Non Finnish (NFE)

AF:

0.644

AC:

691540

AN:

1074650

Other (OTH)

AF:

0.541

AC:

31685

AN:

58570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

16265

32529

48794

65058

81323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17738

35476

53214

70952

88690

<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:

0.476

AC:

72417

AN:

152092

Hom.:

19790

Cov.:

AF XY:

0.463

AC XY:

34453

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.263

AC:

10935

AN:

41500

American (AMR)

AF:

0.396

AC:

6054

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2039

AN:

3470

East Asian (EAS)

AF:

0.0781

AC:

404

AN:

5174

South Asian (SAS)

AF:

0.326

AC:

1567

AN:

4812

European-Finnish (FIN)

AF:

0.577

AC:

6107

AN:

10588

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.642

AC:

43648

AN:

67958

Other (OTH)

AF:

0.497

AC:

1049

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1700

3401

5101

6802

8502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.591

Hom.:

21666

Bravo

AF:

0.450

Asia WGS

AF:

0.206

AC:

718

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.6

(source)

DANN

Benign

0.79

PhyloP100

-0.34

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over