rs3819141

Positions:

• chr21-42137449-T-A

Variant summary

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

The ENST00000408910.7(UMODL1):​c.3786T>A​(p.Pro1262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,613,920 control chromosomes in the GnomAD database, including 110,668 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 0.33 (8875 hom., cov: 34)
  • Exomes 𝑓: 0.37 (101793 hom.)
• Consequence: UMODL1 ENST00000408910.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-1.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3786T>A	p.Pro1262=	synonymous_variant	22/23	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3786T>A	p.Pro1262=	synonymous_variant	22/23	1	NM_001004416.3	ENSP00000386147	P2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50869 AN: 152106 Hom.: 8867 Cov.: 34

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.325

GnomAD3 exomes AF: 0.377 AC: 94141 AN: 249482 Hom.: 18016 AF XY: 0.383 AC XY: 51814 AN XY: 135352

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.374

Gnomad ASJ exome AF: 0.394

Gnomad EAS exome AF: 0.401

Gnomad SAS exome AF: 0.432

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.372

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.371 AC: 542266 AN: 1461696 Hom.: 101793 Cov.: 53 AF XY: 0.374 AC XY: 271809 AN XY: 727156

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.334 AC: 50888 AN: 152224 Hom.: 8875 Cov.: 34 AF XY: 0.337 AC XY: 25062 AN XY: 74420

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.326

Alfa AF: 0.364 Hom.: 3364

Bravo AF: 0.325

Asia WGS AF: 0.393 AC: 1365 AN: 3478

EpiCase AF: 0.375

EpiControl AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.089
DANN	Benign	0.46

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: rs3819141; hg19: chr21-43557559; COSMIC: COSV68569410;