Variant rs4506906 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
UMOD	NM_003361.4 link	c.1182+50C>T		intron_variant		ENST00000396138.9	NP_003352.2	P07911-1

Ensembl

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

GnomAD3 exomes

AF:

0.480

AC:

116820

AN:

243604

Hom.:

32604

AF XY:

0.490

AC XY:

64711

AN XY:

132174

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 SAS exome

AF:

0.352

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

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.0580

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.589

Gnomad4 NFE exome

AF:

0.644

Gnomad4 OTH exome

AF:

0.541

GnomAD4 genome

AF:

0.476

AC:

72417

AN:

152092

Hom.:

19790

Cov.:

AF XY:

0.463

AC XY:

34453

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.396

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.0781

Gnomad4 SAS

AF:

0.326

Gnomad4 FIN

AF:

0.577

Gnomad4 NFE

AF:

0.642

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.590

Hom.:

16365

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.6

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over