21-42072759-A-G

Variant names:

• chr21-42072759-A-G
• rs220279
• NM_001004416.3:c.76+1367A>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.76+1367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,126 control chromosomes in the GnomAD database, including 49,119 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 0.80 (49119 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.837
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.76+1367A>G		intron_variant	Intron 1 of 22	ENST00000408910.7	NP_001004416.3
UMODL1	NM_173568.4	c.76+1367A>G		intron_variant	Intron 1 of 21		NP_775839.4
UMODL1	NM_001199527.3	c.-140-3246A>G		intron_variant	Intron 1 of 21		NP_001186456.2
UMODL1	NM_001199528.4	c.-140-3246A>G		intron_variant	Intron 1 of 22		NP_001186457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.76+1367A>G		intron_variant	Intron 1 of 22	1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.76+1367A>G		intron_variant	Intron 1 of 21	1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.-140-3246A>G		intron_variant	Intron 1 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.-140-3246A>G		intron_variant	Intron 1 of 22	1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121711 AN: 152008 Hom.: 49073 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.801 AC: 121816 AN: 152126 Hom.: 49119 Cov.: 32 AF XY: 0.799 AC XY: 59415 AN XY: 74372

African (AFR) AF: 0.723 AC: 30001 AN: 41490

American (AMR) AF: 0.882 AC: 13501 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2852 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3243 AN: 5152

South Asian (SAS) AF: 0.726 AC: 3494 AN: 4814

European-Finnish (FIN) AF: 0.788 AC: 8338 AN: 10586

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57729 AN: 67990

Other (OTH) AF: 0.816 AC: 1724 AN: 2114

Alfa AF: 0.840 Hom.: 66447

Bravo AF: 0.806

Asia WGS AF: 0.658 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.46
PhyloP100		-0.84
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: rs220279; hg19: chr21-43492868;