rs220161

Variant names:

• chr21-42129183-C-G
• rs220161
• NM_001004416.3:c.3691-530C>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.3691-530C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,074 control chromosomes in the GnomAD database, including 46,260 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 0.77 (46260 hom., cov: 30)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.879 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.3691-530C>G		intron	N/A	NP_001004416.3
	UMODL1	NM_173568.4		c.4075-530C>G		intron	N/A	NP_775839.4
	UMODL1	NM_001199527.3		c.3859-530C>G		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.3691-530C>G		intron	N/A	ENSP00000386147.2
	UMODL1	ENST00000408989.6	TSL:1	c.4075-530C>G		intron	N/A	ENSP00000386126.2
	UMODL1	ENST00000400427.5	TSL:1	c.3859-530C>G		intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116440 AN: 151956 Hom.: 46244 Cov.: 30

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.885

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.766 AC: 116490 AN: 152074 Hom.: 46260 Cov.: 30 AF XY: 0.758 AC XY: 56362 AN XY: 74320

African (AFR) AF: 0.559 AC: 23170 AN: 41442

American (AMR) AF: 0.814 AC: 12452 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3249 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2739 AN: 5162

South Asian (SAS) AF: 0.742 AC: 3566 AN: 4806

European-Finnish (FIN) AF: 0.788 AC: 8346 AN: 10586

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.885 AC: 60151 AN: 67998

Other (OTH) AF: 0.799 AC: 1690 AN: 2114

Alfa AF: 0.811 Hom.: 6344

Bravo AF: 0.759

Asia WGS AF: 0.623 AC: 2171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.62
PhyloP100		0.15
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: rs220161; hg19: chr21-43549293;