21-42088691-C-G

Variant names:

• chr21-42088691-C-G
• rs220301
• NM_001004416.3:c.790+211C>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.790+211C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,994 control chromosomes in the GnomAD database, including 5,610 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 0.26 (5610 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.790+211C>G		intron_variant	Intron 5 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.790+211C>G		intron_variant	Intron 5 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39723 AN: 151876 Hom.: 5612 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.261 AC: 39735 AN: 151994 Hom.: 5610 Cov.: 32 AF XY: 0.260 AC XY: 19320 AN XY: 74270

African (AFR) AF: 0.151 AC: 6251 AN: 41464

American (AMR) AF: 0.328 AC: 5012 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3468

East Asian (EAS) AF: 0.403 AC: 2075 AN: 5152

South Asian (SAS) AF: 0.190 AC: 914 AN: 4810

European-Finnish (FIN) AF: 0.285 AC: 3005 AN: 10542

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20529 AN: 67966

Other (OTH) AF: 0.283 AC: 596 AN: 2108

Alfa AF: 0.158 Hom.: 334

Bravo AF: 0.266

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.062
DANN	Benign	0.47
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs220301; hg19: chr21-43508801;