rs220285

Positions:

• chr21-42075908-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.77-97C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,544,070 control chromosomes in the GnomAD database, including 279,276 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 0.57 (25114 hom., cov: 35)
  • Exomes 𝑓: 0.60 (254162 hom.)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.77-97C>G		intron_variant		ENST00000408910.7	NP_001004416.3
UMODL1	NM_001199527.3	c.-140-97C>G		intron_variant			NP_001186456.2
UMODL1	NM_001199528.4	c.-140-97C>G		intron_variant			NP_001186457.3
UMODL1	NM_173568.4	c.77-97C>G		intron_variant			NP_775839.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.77-97C>G		intron_variant		1	NM_001004416.3	ENSP00000386147	P2
UMODL1	ENST00000400424.6	c.-140-97C>G		intron_variant		1		ENSP00000383276	A2
UMODL1	ENST00000400427.5	c.-140-97C>G		intron_variant		1		ENSP00000383279	A2
UMODL1	ENST00000408989.6	c.77-97C>G		intron_variant		1		ENSP00000386126	A2

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86194 AN: 152126 Hom.: 25089 Cov.: 35

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.598 AC: 831694 AN: 1391826 Hom.: 254162 AF XY: 0.595 AC XY: 407905 AN XY: 685608

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.567 AC: 86257 AN: 152244 Hom.: 25114 Cov.: 35 AF XY: 0.561 AC XY: 41730 AN XY: 74446

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.572

Alfa AF: 0.596 Hom.: 3412

Bravo AF: 0.563

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.034
DANN	Benign	0.38

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: rs220285; hg19: chr21-43496017; COSMIC: COSV68576088;