rs2839470

chr21-42128129-T-C

Variant summary

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

The NM_001004416.3(UMODL1):c.3690+298T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 531,924 control chromosomes in the GnomAD database, including 84,573 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 0.54 (22299 hom., cov: 33)
  • Exomes 𝑓: 0.57 (62274 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.3690+298T>C		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.3690+298T>C		intron_variant		1	NM_001004416.3	P2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81743 AN: 152046 Hom.: 22303 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.571 AC: 216828 AN: 379758 Hom.: 62274 Cov.: 2 AF XY: 0.569 AC XY: 120124 AN XY: 210966

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.630

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.537 AC: 81775 AN: 152166 Hom.: 22299 Cov.: 33 AF XY: 0.535 AC XY: 39816 AN XY: 74370

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.526

Alfa AF: 0.569 Hom.: 33543

Bravo AF: 0.527

Asia WGS AF: 0.551 AC: 1918 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	0.025
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2839470; hg19: chr21-43548239; COSMIC: COSV68570282; COSMIC: COSV68570282;