21-42118692-G-A

Position:

• chr21-42118692-G-A

Variant summary

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

The NM_001004416.3(UMODL1):​c.2476-419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,920 control chromosomes in the GnomAD database, including 3,354 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 0.21 (3354 hom., cov: 31)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.2476-419G>A		intron_variant		ENST00000408910.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.2476-419G>A		intron_variant		1	NM_001004416.3	P2
UMODL1	ENST00000400424.6	c.2260-419G>A		intron_variant		1		A2
UMODL1	ENST00000400427.5	c.2644-419G>A		intron_variant		1		A2
UMODL1	ENST00000408989.6	c.2860-419G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31332 AN: 151802 Hom.: 3344 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.206 AC: 31361 AN: 151920 Hom.: 3354 Cov.: 31 AF XY: 0.208 AC XY: 15470 AN XY: 74250

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.207

Alfa AF: 0.181 Hom.: 917

Bravo AF: 0.211

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.51

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: rs220145; hg19: chr21-43538802; COSMIC: COSV68570485; COSMIC: COSV68570485;