rs915840

Positions:

• chr21-42140761-T-C

Variant summary

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

The NM_001004416.3(UMODL1):​c.*22-1335T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,100 control chromosomes in the GnomAD database, including 2,700 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 0.19 (2700 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

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 (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.*22-1335T>C		intron_variant		ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.*22-1335T>C		intron_variant		1	NM_001004416.3	ENSP00000386147	P2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28353 AN: 151982 Hom.: 2696 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.186 AC: 28365 AN: 152100 Hom.: 2700 Cov.: 32 AF XY: 0.190 AC XY: 14147 AN XY: 74376

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.174

Alfa AF: 0.185 Hom.: 335

Bravo AF: 0.180

Asia WGS AF: 0.270 AC: 940 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	0.81
DANN	Benign	0.47

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: rs915840; hg19: chr21-43560871;