21-42109106-G-C

Variant names:

• chr21-42109106-G-C
• rs34212454
• NM_001004416.3:c.1520-456G>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.1520-456G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.22 (4455 hom., cov: 17)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.283 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.1520-456G>C		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.1520-456G>C		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.1304-456G>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.1520-456G>C		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.1520-456G>C		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.1304-456G>C		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 20158 AN: 93650 Hom.: 4449 Cov.: 17

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.215 AC: 20185 AN: 93670 Hom.: 4455 Cov.: 17 AF XY: 0.218 AC XY: 9748 AN XY: 44804

African (AFR) AF: 0.289 AC: 6007 AN: 20806

American (AMR) AF: 0.235 AC: 2182 AN: 9270

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 565 AN: 2486

East Asian (EAS) AF: 0.221 AC: 617 AN: 2798

South Asian (SAS) AF: 0.196 AC: 483 AN: 2470

European-Finnish (FIN) AF: 0.145 AC: 777 AN: 5376

Middle Eastern (MID) AF: 0.167 AC: 21 AN: 126

European-Non Finnish (NFE) AF: 0.188 AC: 9121 AN: 48484

Other (OTH) AF: 0.217 AC: 290 AN: 1338

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.13
PhyloP100		-2.5
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: rs34212454; hg19: chr21-43529216;