21-42117384-A-G

Variant summary

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

The NM_001004416.3(UMODL1):c.2475+1399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,118 control chromosomes in the GnomAD database, including 31,767 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 0.64 (31767 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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 (SAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.2475+1399A>G		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.2475+1399A>G		intron_variant		1	NM_001004416.3	P2
UMODL1	ENST00000400424.6	c.2259+1399A>G		intron_variant		1		A2
UMODL1	ENST00000400427.5	c.2643+1399A>G		intron_variant		1		A2
UMODL1	ENST00000408989.6	c.2859+1399A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97966 AN: 152002 Hom.: 31734 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.645 AC: 98050 AN: 152118 Hom.: 31767 Cov.: 32 AF XY: 0.643 AC XY: 47827 AN XY: 74372

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.657

Alfa AF: 0.639 Hom.: 13109

Bravo AF: 0.654

Asia WGS AF: 0.705 AC: 2450 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	0.094
Dann	Benign	0.55

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: rs220143; hg19: chr21-43537494;