rs220181

Variant names:

• chr21-42141358-A-G
• rs220181
• NM_001004416.3:c.*22-738A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(UMODL1):​c.*22-738A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,974 control chromosomes in the GnomAD database, including 22,334 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 (22334 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 1 publications found

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]

ENSG00000304334 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.*22-738A>G		intron_variant	Intron 22 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.*22-738A>G		intron_variant	Intron 22 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81556 AN: 151856 Hom.: 22316 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.537 AC: 81623 AN: 151974 Hom.: 22334 Cov.: 32 AF XY: 0.539 AC XY: 40055 AN XY: 74308

African (AFR) AF: 0.429 AC: 17752 AN: 41424

American (AMR) AF: 0.599 AC: 9155 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2083 AN: 3466

East Asian (EAS) AF: 0.738 AC: 3820 AN: 5174

South Asian (SAS) AF: 0.541 AC: 2610 AN: 4820

European-Finnish (FIN) AF: 0.600 AC: 6334 AN: 10548

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37975 AN: 67952

Other (OTH) AF: 0.547 AC: 1153 AN: 2108

Alfa AF: 0.551 Hom.: 3102

Bravo AF: 0.534

Asia WGS AF: 0.626 AC: 2175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.43
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs220181; hg19: chr21-43561468;