21-42134346-C-T

Variant names:

• chr21-42134346-C-T
• rs2839471
• NM_001004416.3:c.3776-3093C>T

Variant summary

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

The NM_001004416.3(UMODL1):​c.3776-3093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,126 control chromosomes in the GnomAD database, including 11,779 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 0.39 (11779 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	NM_001004416.3	MANE Select	c.3776-3093C>T		intron	N/A	NP_001004416.3	Q5DID0-1
	UMODL1	NM_173568.4		c.4160-3093C>T		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3944-3093C>T		intron	N/A	NP_001186456.2	Q5DID0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.3776-3093C>T		intron	N/A	ENSP00000386147.2	Q5DID0-1
	UMODL1	ENST00000408989.6	TSL:1	c.4160-3093C>T		intron	N/A	ENSP00000386126.2	Q5DID0-2
	UMODL1	ENST00000400427.5	TSL:1	c.3944-3093C>T		intron	N/A	ENSP00000383279.1	Q5DID0-4

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59067 AN: 152008 Hom.: 11774 Cov.: 33

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.388 AC: 59097 AN: 152126 Hom.: 11779 Cov.: 33 AF XY: 0.388 AC XY: 28877 AN XY: 74340

African (AFR) AF: 0.321 AC: 13327 AN: 41498

American (AMR) AF: 0.406 AC: 6199 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2629 AN: 5172

South Asian (SAS) AF: 0.397 AC: 1910 AN: 4816

European-Finnish (FIN) AF: 0.377 AC: 3985 AN: 10558

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28513 AN: 68004

Other (OTH) AF: 0.409 AC: 865 AN: 2116

Alfa AF: 0.414 Hom.: 25128

Bravo AF: 0.387

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.2
DANN	Benign	0.48
PhyloP100		-0.11
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: rs2839471; hg19: chr21-43554456;