rs13051533

Positions:

• chr21-42125379-G-A
• chr21-42125379-G-T
• chr21-42125379-G-C

Variant summary

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

The NM_001004416.3(UMODL1):​c.3148-966G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,916 control chromosomes in the GnomAD database, including 16,628 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 0.45 (16628 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

Genes affected

UMODL1 (HGNC:12560): (uromodulin like 1) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in neutrophil migration. Predicted to act upstream of or within several processes, including adipose tissue development; cellular response to gonadotropin-releasing hormone; and regulation of ovarian follicle development. Predicted to be located in cytoplasm and external side of plasma membrane. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane; cell surface; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

UMODL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3148-966G>A		intron_variant		ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3148-966G>A		intron_variant		1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68239 AN: 151798 Hom.: 16636 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.449 AC: 68240 AN: 151916 Hom.: 16628 Cov.: 32 AF XY: 0.448 AC XY: 33289 AN XY: 74248

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.438

Alfa AF: 0.515 Hom.: 19799

Bravo AF: 0.429

Asia WGS AF: 0.449 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.56

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: rs13051533; hg19: chr21-43545489;