rs220282

Variant names:

• chr21-42073647-A-G
• rs220282
• NM_001004416.3:c.76+2255A>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.76+2255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,070 control chromosomes in the GnomAD database, including 41,168 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 0.73 (41168 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.76+2255A>G		intron_variant	Intron 1 of 22	ENST00000408910.7	NP_001004416.3
UMODL1	NM_173568.4	c.76+2255A>G		intron_variant	Intron 1 of 21		NP_775839.4
UMODL1	NM_001199527.3	c.-140-2358A>G		intron_variant	Intron 1 of 21		NP_001186456.2
UMODL1	NM_001199528.4	c.-140-2358A>G		intron_variant	Intron 1 of 22		NP_001186457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.76+2255A>G		intron_variant	Intron 1 of 22	1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.76+2255A>G		intron_variant	Intron 1 of 21	1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.-140-2358A>G		intron_variant	Intron 1 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.-140-2358A>G		intron_variant	Intron 1 of 22	1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111562 AN: 151952 Hom.: 41137 Cov.: 32

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.734 AC: 111645 AN: 152070 Hom.: 41168 Cov.: 32 AF XY: 0.733 AC XY: 54519 AN XY: 74340

African (AFR) AF: 0.679 AC: 28150 AN: 41436

American (AMR) AF: 0.823 AC: 12579 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2476 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3144 AN: 5178

South Asian (SAS) AF: 0.639 AC: 3079 AN: 4820

European-Finnish (FIN) AF: 0.756 AC: 7995 AN: 10580

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51815 AN: 67984

Other (OTH) AF: 0.731 AC: 1545 AN: 2114

Alfa AF: 0.751 Hom.: 130821

Bravo AF: 0.739

Asia WGS AF: 0.608 AC: 2117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0080
DANN	Benign	0.45
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs220282; hg19: chr21-43493756;