rs220170

Positions:

• chr21-42135190-C-T
• chr21-42135190-C-G

Variant summary

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

The NM_001004416.3(UMODL1):​c.3776-2249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,276 control chromosomes in the GnomAD database, including 8,901 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 (8901 hom., cov: 34)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.3776-2249C>T		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.3776-2249C>T		intron_variant		1	NM_001004416.3	P2

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50228 AN: 152158 Hom.: 8901 Cov.: 34

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50254 AN: 152276 Hom.: 8901 Cov.: 34 AF XY: 0.324 AC XY: 24116 AN XY: 74456

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.334

Alfa AF: 0.378 Hom.: 10231

Bravo AF: 0.323

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.52

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: rs220170; hg19: chr21-43555300;