21-42120350-G-T

Variant names:

• chr21-42120350-G-T
• rs220149
• NM_001004416.3:c.2690-737G>T

Variant summary

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

The NM_173568.4(UMODL1):​c.3074-737G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,106 control chromosomes in the GnomAD database, including 24,570 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 0.56 (24570 hom., cov: 34)
• Consequence: UMODL1 NM_173568.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173568.4. 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.2690-737G>T		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.3074-737G>T		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.2858-737G>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.2690-737G>T		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.3074-737G>T		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.2858-737G>T		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85657 AN: 151988 Hom.: 24547 Cov.: 34

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.564 AC: 85732 AN: 152106 Hom.: 24570 Cov.: 34 AF XY: 0.561 AC XY: 41688 AN XY: 74354

African (AFR) AF: 0.483 AC: 20051 AN: 41488

American (AMR) AF: 0.658 AC: 10068 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2313 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2693 AN: 5176

South Asian (SAS) AF: 0.613 AC: 2958 AN: 4824

European-Finnish (FIN) AF: 0.472 AC: 4986 AN: 10556

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40537 AN: 67982

Other (OTH) AF: 0.596 AC: 1258 AN: 2110

Alfa AF: 0.602 Hom.: 44206

Bravo AF: 0.574

Asia WGS AF: 0.575 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.52
PhyloP100		-1.3
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: rs220149; hg19: chr21-43540460;