rs11911271

Positions:

• chr21-42135381-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.3776-2058T>C 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 152,196 control chromosomes in the GnomAD database, including 4,110 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 (4110 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.3776-2058T>C		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.3776-2058T>C		intron_variant		1	NM_001004416.3	P2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25496 AN: 152078 Hom.: 4079 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.168 AC: 25577 AN: 152196 Hom.: 4110 Cov.: 33 AF XY: 0.170 AC XY: 12636 AN XY: 74416

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.125

Alfa AF: 0.124 Hom.: 347

Bravo AF: 0.178

Asia WGS AF: 0.185 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.68

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: rs11911271; hg19: chr21-43555491;