21-42072594-G-A

Position:

• chr21-42072594-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.76+1202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,034 control chromosomes in the GnomAD database, including 18,722 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 0.49 (18722 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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 (AMR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UMODL1	NM_001004416.3	c.76+1202G>A		intron_variant		ENST00000408910.7
UMODL1	NM_001199527.3	c.-140-3411G>A		intron_variant
UMODL1	NM_001199528.4	c.-140-3411G>A		intron_variant
UMODL1	NM_173568.4	c.76+1202G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UMODL1	ENST00000408910.7	c.76+1202G>A		intron_variant		1	NM_001004416.3	P2
UMODL1	ENST00000400424.6	c.-140-3411G>A		intron_variant		1		A2
UMODL1	ENST00000400427.5	c.-140-3411G>A		intron_variant		1		A2
UMODL1	ENST00000408989.6	c.76+1202G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74388 AN: 151916 Hom.: 18691 Cov.: 33

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.490 AC: 74461 AN: 152034 Hom.: 18722 Cov.: 33 AF XY: 0.485 AC XY: 36035 AN XY: 74316

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.514

Alfa AF: 0.505 Hom.: 25937

Bravo AF: 0.511

Asia WGS AF: 0.392 AC: 1363 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	5.4
DANN	Benign	0.45

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: rs220278; hg19: chr21-43492703;