21-42128867-G-A

Variant names:

• chr21-42128867-G-A
• rs4920063
• NM_001004416.3:c.3691-846G>A

Variant summary

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

The NM_001004416.3(UMODL1):​c.3691-846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,046 control chromosomes in the GnomAD database, including 16,892 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 0.46 (16892 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.839
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3691-846G>A		intron_variant	Intron 20 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3691-846G>A		intron_variant	Intron 20 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69764 AN: 151924 Hom.: 16901 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.459 AC: 69763 AN: 152046 Hom.: 16892 Cov.: 32 AF XY: 0.454 AC XY: 33745 AN XY: 74298

African (AFR) AF: 0.303 AC: 12571 AN: 41472

American (AMR) AF: 0.446 AC: 6811 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2018 AN: 3468

East Asian (EAS) AF: 0.363 AC: 1877 AN: 5166

South Asian (SAS) AF: 0.428 AC: 2062 AN: 4814

European-Finnish (FIN) AF: 0.521 AC: 5509 AN: 10570

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37311 AN: 67972

Other (OTH) AF: 0.470 AC: 992 AN: 2110

Alfa AF: 0.496 Hom.: 4958

Bravo AF: 0.446

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.59
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: rs4920063; hg19: chr21-43548977;