rs220308

Positions:

• chr21-42096479-G-T
• chr21-42096479-G-A

Variant summary

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

The NM_001004416.3(UMODL1):​c.932-2447G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,988 control chromosomes in the GnomAD database, including 15,109 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 (15109 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.932-2447G>T		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.932-2447G>T		intron_variant		1	NM_001004416.3	P2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65297 AN: 151870 Hom.: 15108 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.430 AC: 65325 AN: 151988 Hom.: 15109 Cov.: 32 AF XY: 0.431 AC XY: 31984 AN XY: 74284

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.458

Alfa AF: 0.467 Hom.: 2206

Bravo AF: 0.421

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.98
DANN	Benign	0.42

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: rs220308; hg19: chr21-43516589;