rs220131

Positions:

• chr21-42111738-C-T

Variant summary

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

The NM_001004416.3(UMODL1):​c.2104+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,579,198 control chromosomes in the GnomAD database, including 201,737 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 0.43 (15308 hom., cov: 33)
  • Exomes 𝑓: 0.51 (186429 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.2104+28C>T		intron_variant		ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.2104+28C>T		intron_variant		1	NM_001004416.3	ENSP00000386147	P2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65321 AN: 151958 Hom.: 15316 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.455

GnomAD3 exomes AF: 0.479 AC: 105189 AN: 219374 Hom.: 25676 AF XY: 0.479 AC XY: 56837 AN XY: 118580

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.477

Gnomad EAS exome AF: 0.498

Gnomad SAS exome AF: 0.393

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.502

GnomAD4 exome AF: 0.507 AC: 723923 AN: 1427120 Hom.: 186429 Cov.: 32 AF XY: 0.504 AC XY: 356158 AN XY: 706612

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.477

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.430 AC: 65321 AN: 152078 Hom.: 15308 Cov.: 33 AF XY: 0.430 AC XY: 31961 AN XY: 74330

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.451

Alfa AF: 0.454 Hom.: 3467

Bravo AF: 0.417

Asia WGS AF: 0.444 AC: 1547 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.57

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: rs220131; hg19: chr21-43531848; COSMIC: COSV61160521; COSMIC: COSV61160521;