rs9928936

Positions:

• chr16-20341727-G-A
• chr16-20341727-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003361.4(UMOD):​c.1332-391C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,114 control chromosomes in the GnomAD database, including 2,132 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 0.16 (2132 hom., cov: 33)
• Consequence: UMOD NM_003361.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMOD	NM_003361.4	c.1332-391C>T		intron_variant		ENST00000396138.9	NP_003352.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMOD	ENST00000396138.9	c.1332-391C>T		intron_variant		5	NM_003361.4	ENSP00000379442.5
UMOD	ENST00000396134.6	c.1431-391C>T		intron_variant		2		ENSP00000379438.2
UMOD	ENST00000570689.5	c.1332-391C>T		intron_variant		5		ENSP00000460548.1
UMOD	ENST00000570331.1	n.97-391C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24684 AN: 151996 Hom.: 2121 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.162 AC: 24714 AN: 152114 Hom.: 2132 Cov.: 33 AF XY: 0.164 AC XY: 12185 AN XY: 74324

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.167

Alfa AF: 0.166 Hom.: 425

Bravo AF: 0.158

Asia WGS AF: 0.123 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.1
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs9928936; hg19: chr16-20353049;