21-42109405-G-C

Variant names:

• chr21-42109405-G-C
• rs220120
• NM_001004416.3:c.1520-157G>C

Variant summary

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

The NM_001004416.3(UMODL1):​c.1520-157G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,040 control chromosomes in the GnomAD database, including 27,749 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 0.60 (27749 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 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.1520-157G>C		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.1520-157G>C		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.1304-157G>C		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.1520-157G>C		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.1520-157G>C		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.1304-157G>C		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91529 AN: 151922 Hom.: 27702 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.603 AC: 91638 AN: 152040 Hom.: 27749 Cov.: 32 AF XY: 0.606 AC XY: 45061 AN XY: 74314

African (AFR) AF: 0.596 AC: 24688 AN: 41444

American (AMR) AF: 0.665 AC: 10162 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 2170 AN: 3472

East Asian (EAS) AF: 0.707 AC: 3661 AN: 5178

South Asian (SAS) AF: 0.638 AC: 3081 AN: 4830

European-Finnish (FIN) AF: 0.593 AC: 6243 AN: 10534

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39573 AN: 67978

Other (OTH) AF: 0.604 AC: 1276 AN: 2112

Alfa AF: 0.594 Hom.: 3340

Bravo AF: 0.610

Asia WGS AF: 0.642 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.48
PhyloP100		-0.59
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: rs220120; hg19: chr21-43529515;