21-42109106-G-C

Position:

• chr21-42109106-G-C

Variant summary

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

The NM_001004416.3(UMODL1):​c.1520-456G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.22 (4455 hom., cov: 17)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.1520-456G>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.1520-456G>C		intron_variant		1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.1520-456G>C		intron_variant		1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.1304-456G>C		intron_variant		1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.1304-456G>C		intron_variant		1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 20158 AN: 93650 Hom.: 4449 Cov.: 17

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.215 AC: 20185 AN: 93670 Hom.: 4455 Cov.: 17 AF XY: 0.218 AC XY: 9748 AN XY: 44804

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.217

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.13

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: rs34212454; hg19: chr21-43529216;