rs4920063

Positions:

• chr21-42128867-G-A
• chr21-42128867-G-T
• chr21-42128867-G-C

Variant summary

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

The ENST00000408910.7(UMODL1):​c.3691-846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,046 control chromosomes in the GnomAD database, including 16,892 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 0.46 (16892 hom., cov: 32)
• Consequence: UMODL1 ENST00000408910.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.839

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3691-846G>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.3691-846G>A		intron_variant		1	NM_001004416.3	ENSP00000386147	P2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69764 AN: 151924 Hom.: 16901 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.459 AC: 69763 AN: 152046 Hom.: 16892 Cov.: 32 AF XY: 0.454 AC XY: 33745 AN XY: 74298

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.470

Alfa AF: 0.496 Hom.: 4958

Bravo AF: 0.446

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.59

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: rs4920063; hg19: chr21-43548977;