rs220120

chr21-42109405-G-Cchr21-42109405-G-A

Variant summary

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

The NM_001004416.3(UMODL1):c.1520-157G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,040 control chromosomes in the GnomAD database, including 27,749 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 0.60 (27749 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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]

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 (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.1520-157G>C		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.1520-157G>C		intron_variant		1	NM_001004416.3	P2
UMODL1	ENST00000400424.6	c.1304-157G>C		intron_variant		1		A2
UMODL1	ENST00000400427.5	c.1304-157G>C		intron_variant		1		A2
UMODL1	ENST00000408989.6	c.1520-157G>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91529 AN: 151922 Hom.: 27702 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.603 AC: 91638 AN: 152040 Hom.: 27749 Cov.: 32 AF XY: 0.606 AC XY: 45061 AN XY: 74314

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.604

Alfa AF: 0.594 Hom.: 3340

Bravo AF: 0.610

Asia WGS AF: 0.642 AC: 2230 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	0.26
Dann	Benign	0.48

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: rs220120; hg19: chr21-43529515;