21-42072220-G-A

Position:

• chr21-42072220-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+828G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,124 control chromosomes in the GnomAD database, including 38,440 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 0.70 (38440 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.76+828G>A		intron_variant		ENST00000408910.7	NP_001004416.3
UMODL1	NM_173568.4	c.76+828G>A		intron_variant			NP_775839.4
UMODL1	NM_001199527.3	c.-140-3785G>A		intron_variant			NP_001186456.2
UMODL1	NM_001199528.4	c.-140-3785G>A		intron_variant			NP_001186457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.76+828G>A		intron_variant		1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.76+828G>A		intron_variant		1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.-140-3785G>A		intron_variant		1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.-140-3785G>A		intron_variant		1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106766 AN: 152006 Hom.: 38412 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.702 AC: 106835 AN: 152124 Hom.: 38440 Cov.: 33 AF XY: 0.699 AC XY: 51975 AN XY: 74384

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.723

Alfa AF: 0.767 Hom.: 92314

Bravo AF: 0.704

Asia WGS AF: 0.532 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.46

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: rs220276; hg19: chr21-43492329;