rs220179

Positions:

• chr21-42139923-C-T

Variant summary

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

The NM_001004416.3(UMODL1):​c.*22-2173C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,112 control chromosomes in the GnomAD database, including 2,457 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 0.17 (2457 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.*22-2173C>T		intron_variant		ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.*22-2173C>T		intron_variant		1	NM_001004416.3	ENSP00000386147	P2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25512 AN: 151994 Hom.: 2449 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.168 AC: 25544 AN: 152112 Hom.: 2457 Cov.: 32 AF XY: 0.169 AC XY: 12536 AN XY: 74348

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.198

Alfa AF: 0.188 Hom.: 4085

Bravo AF: 0.170

Asia WGS AF: 0.218 AC: 757 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	2.9
DANN	Benign	0.61

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: rs220179; hg19: chr21-43560033;