21-42096479-G-T

Variant names:

• chr21-42096479-G-T
• rs220308
• NM_001004416.3:c.932-2447G>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.932-2447G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,988 control chromosomes in the GnomAD database, including 15,109 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 0.43 (15109 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 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.932-2447G>T		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.932-2447G>T		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.716-2447G>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.932-2447G>T		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.932-2447G>T		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.716-2447G>T		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65297 AN: 151870 Hom.: 15108 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.430 AC: 65325 AN: 151988 Hom.: 15109 Cov.: 32 AF XY: 0.431 AC XY: 31984 AN XY: 74284

African (AFR) AF: 0.247 AC: 10251 AN: 41454

American (AMR) AF: 0.471 AC: 7194 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3466

East Asian (EAS) AF: 0.543 AC: 2803 AN: 5160

South Asian (SAS) AF: 0.389 AC: 1878 AN: 4822

European-Finnish (FIN) AF: 0.518 AC: 5459 AN: 10534

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

European-Non Finnish (NFE) AF: 0.509 AC: 34599 AN: 67972

Other (OTH) AF: 0.458 AC: 965 AN: 2106

Alfa AF: 0.467 Hom.: 2206

Bravo AF: 0.421

Asia WGS AF: 0.446 AC: 1550 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	0.98
DANN	Benign	0.42
PhyloP100		-0.056
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: rs220308; hg19: chr21-43516589;