Variant chr16-20350628-C-T 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.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

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=-0.95).

BP6

Variant 16-20350628-C-T is Benign according to our data. Variant chr16-20350628-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMOD	NM_003361.4 linkuse as main transcript	c.88+22G>A		intron_variant		ENST00000396138.9	NP_003352.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMOD	ENST00000396138.9 linkuse as main transcript	c.88+22G>A		intron_variant		5	NM_003361.4	ENSP00000379442	P2	P07911-1

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

GnomAD3 exomes

AF:

0.139

AC:

34711

AN:

249662

Hom.:

2867

AF XY:

0.143

AC XY:

19282

AN XY:

135076

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 SAS exome

AF:

0.139

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

Gnomad4 AFR exome

AF:

0.0256

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.00335

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.123

AC:

18734

AN:

152206

Hom.:

1514

Cov.:

AF XY:

0.126

AC XY:

9342

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.00522

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.140

Hom.:

314

Bravo

AF:

0.113

Asia WGS

AF:

0.0710

AC:

248

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	clinical testing	GeneDx	Jul 17, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.82

DANN

Benign

0.46

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