rs749020

Variant names:

• chr21-42086375-A-G
• rs749020
• NM_001004416.3:c.603+963A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(UMODL1):​c.603+963A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,984 control chromosomes in the GnomAD database, including 29,043 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 0.62 (29043 hom., cov: 34)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.603+963A>G		intron_variant	Intron 4 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.603+963A>G		intron_variant	Intron 4 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93772 AN: 151866 Hom.: 29009 Cov.: 34

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.618 AC: 93856 AN: 151984 Hom.: 29043 Cov.: 34 AF XY: 0.620 AC XY: 46039 AN XY: 74248

African (AFR) AF: 0.643 AC: 26649 AN: 41446

American (AMR) AF: 0.604 AC: 9232 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2778 AN: 5166

South Asian (SAS) AF: 0.680 AC: 3269 AN: 4808

European-Finnish (FIN) AF: 0.633 AC: 6679 AN: 10556

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40932 AN: 67944

Other (OTH) AF: 0.609 AC: 1283 AN: 2108

Alfa AF: 0.614 Hom.: 17850

Bravo AF: 0.612

Asia WGS AF: 0.625 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.31
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs749020; hg19: chr21-43506485;