21-42102540-C-A

Position:

• chr21-42102540-C-A

Variant summary

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

The NM_001004416.3(UMODL1):​c.1299+262C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 237,836 control chromosomes in the GnomAD database, including 11,097 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 0.31 (7187 hom., cov: 32)
  • Exomes 𝑓: 0.30 (3910 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.1299+262C>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.1299+262C>A		intron_variant		1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46713 AN: 151986 Hom.: 7181 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.302 AC: 25877 AN: 85732 Hom.: 3910 Cov.: 0 AF XY: 0.300 AC XY: 13173 AN XY: 43868

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.395

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.291

GnomAD4 genome AF: 0.307 AC: 46757 AN: 152104 Hom.: 7187 Cov.: 32 AF XY: 0.305 AC XY: 22686 AN XY: 74354

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.326

Alfa AF: 0.319 Hom.: 8086

Bravo AF: 0.311

Asia WGS AF: 0.326 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.54
DANN	Benign	0.35

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: rs220110; hg19: chr21-43522650;