rs220109

Positions:

• chr21-42102239-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000408910.7(UMODL1):​c.1260T>C​(p.Ser420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,612,020 control chromosomes in the GnomAD database, including 237,068 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 0.52 (20848 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216220 hom.)
• Consequence: UMODL1 ENST00000408910.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448

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-AS1 (HGNC:23821): (UMODL1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=0.448 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.1260T>C	p.Ser420=	synonymous_variant	8/23	ENST00000408910.7	NP_001004416.3
UMODL1-AS1	NR_027243.1	n.2036A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.1260T>C	p.Ser420=	synonymous_variant	8/23	1	NM_001004416.3	ENSP00000386147	P2
UMODL1-AS1	ENST00000329015.2	n.2036A>G		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79319 AN: 151910 Hom.: 20811 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.510

GnomAD3 exomes AF: 0.555 AC: 138340 AN: 249056 Hom.: 38911 AF XY: 0.552 AC XY: 74631 AN XY: 135140

Gnomad AFR exome AF: 0.461

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.540

Gnomad EAS exome AF: 0.579

Gnomad SAS exome AF: 0.549

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.536

Gnomad OTH exome AF: 0.561

GnomAD4 exome AF: 0.543 AC: 793204 AN: 1459994 Hom.: 216220 Cov.: 38 AF XY: 0.543 AC XY: 394351 AN XY: 726240

Gnomad4 AFR exome AF: 0.457

Gnomad4 AMR exome AF: 0.661

Gnomad4 ASJ exome AF: 0.537

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.522 AC: 79407 AN: 152026 Hom.: 20848 Cov.: 32 AF XY: 0.524 AC XY: 38912 AN XY: 74280

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.515

Alfa AF: 0.538 Hom.: 34246

Bravo AF: 0.525

Asia WGS AF: 0.554 AC: 1925 AN: 3478

EpiCase AF: 0.532

EpiControl AF: 0.541

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.50

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: rs220109; hg19: chr21-43522349; COSMIC: COSV61159582;