rs220172

Variant names:

• chr21-42136581-G-A
• rs220172
• NM_001004416.3:c.3776-858G>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.3776-858G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,042 control chromosomes in the GnomAD database, including 3,160 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 0.20 (3160 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 4 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]

ENSG00000304334 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 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.3776-858G>A		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.4160-858G>A		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3944-858G>A		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.3776-858G>A		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.4160-858G>A		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.3944-858G>A		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30132 AN: 151922 Hom.: 3148 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.198 AC: 30177 AN: 152042 Hom.: 3160 Cov.: 32 AF XY: 0.199 AC XY: 14813 AN XY: 74350

African (AFR) AF: 0.178 AC: 7369 AN: 41466

American (AMR) AF: 0.235 AC: 3597 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 867 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1702 AN: 5170

South Asian (SAS) AF: 0.129 AC: 624 AN: 4822

European-Finnish (FIN) AF: 0.199 AC: 2101 AN: 10556

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13137 AN: 67954

Other (OTH) AF: 0.223 AC: 472 AN: 2116

Alfa AF: 0.197 Hom.: 11556

Bravo AF: 0.203

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.78
PhyloP100		-0.48
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: rs220172; hg19: chr21-43556691;