21-42135190-C-T

Variant names:

• chr21-42135190-C-T
• rs220170
• NM_001004416.3:c.3776-2249C>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.3776-2249C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,276 control chromosomes in the GnomAD database, including 8,901 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 0.33 (8901 hom., cov: 34)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.405 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	NM_001004416.3	MANE Select	c.3776-2249C>T		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.4160-2249C>T		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3944-2249C>T		intron	N/A	NP_001186456.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.3776-2249C>T		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.4160-2249C>T		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.3944-2249C>T		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50228 AN: 152158 Hom.: 8901 Cov.: 34

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.330 AC: 50254 AN: 152276 Hom.: 8901 Cov.: 34 AF XY: 0.324 AC XY: 24116 AN XY: 74456

African (AFR) AF: 0.216 AC: 8977 AN: 41548

American (AMR) AF: 0.286 AC: 4386 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1483 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1241 AN: 5178

South Asian (SAS) AF: 0.308 AC: 1489 AN: 4830

European-Finnish (FIN) AF: 0.339 AC: 3591 AN: 10602

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27787 AN: 68016

Other (OTH) AF: 0.334 AC: 707 AN: 2114

Alfa AF: 0.371 Hom.: 13221

Bravo AF: 0.323

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.52
PhyloP100		0.040
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: rs220170; hg19: chr21-43555300;