chr21-42136658-G-C

Variant names:

• chr21-42136658-G-C
• rs220173
• NM_001004416.3:c.3776-781G>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.3776-781G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,074 control chromosomes in the GnomAD database, including 9,858 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 0.35 (9858 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• Publications: 1 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]

ENSG00000304334 (HGNC:):

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 = 0.501 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.3776-781G>C		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.4160-781G>C		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3944-781G>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.3776-781G>C		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.4160-781G>C		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.3944-781G>C		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53186 AN: 151958 Hom.: 9850 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.350 AC: 53238 AN: 152074 Hom.: 9858 Cov.: 33 AF XY: 0.350 AC XY: 26037 AN XY: 74314

African (AFR) AF: 0.239 AC: 9908 AN: 41492

American (AMR) AF: 0.395 AC: 6043 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3464

East Asian (EAS) AF: 0.518 AC: 2673 AN: 5162

South Asian (SAS) AF: 0.251 AC: 1210 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4079 AN: 10536

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26474 AN: 67984

Other (OTH) AF: 0.377 AC: 798 AN: 2114

Alfa AF: 0.225 Hom.: 508

Bravo AF: 0.349

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.013
DANN	Benign	0.26
PhyloP100		-0.83
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: rs220173; hg19: chr21-43556768;