rs220298

Variant names:

• chr21-42079058-A-G
• rs220298
• NM_001004416.3:c.319+2811A>G

Variant summary

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

The NM_001004416.3(UMODL1):​c.319+2811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,258 control chromosomes in the GnomAD database, including 64,298 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 0.92 (64298 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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]

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 (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.319+2811A>G		intron_variant	Intron 2 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.319+2811A>G		intron_variant	Intron 2 of 22	1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.319+2811A>G		intron_variant	Intron 2 of 21	1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.103+2811A>G		intron_variant	Intron 2 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.103+2811A>G		intron_variant	Intron 2 of 22	1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139584 AN: 152140 Hom.: 64235 Cov.: 32

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.936

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.918 AC: 139705 AN: 152258 Hom.: 64298 Cov.: 32 AF XY: 0.916 AC XY: 68211 AN XY: 74438

African (AFR) AF: 0.972 AC: 40412 AN: 41556

American (AMR) AF: 0.925 AC: 14159 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3254 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3575 AN: 5164

South Asian (SAS) AF: 0.905 AC: 4364 AN: 4824

European-Finnish (FIN) AF: 0.907 AC: 9635 AN: 10620

Middle Eastern (MID) AF: 0.938 AC: 274 AN: 292

European-Non Finnish (NFE) AF: 0.902 AC: 61348 AN: 67998

Other (OTH) AF: 0.909 AC: 1919 AN: 2112

Alfa AF: 0.916 Hom.: 87614

Bravo AF: 0.921

Asia WGS AF: 0.813 AC: 2827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.086
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: rs220298; hg19: chr21-43499167;