rs220154

Variant names:

• chr21-42124783-T-C
• rs220154
• NM_001004416.3:c.3148-1562T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-42124783-T-C
• chr21-42124783-T-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.3148-1562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,846 control chromosomes in the GnomAD database, including 22,717 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 0.54 (22717 hom., cov: 31)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3148-1562T>C		intron_variant	Intron 17 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3148-1562T>C		intron_variant	Intron 17 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82458 AN: 151728 Hom.: 22689 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.544 AC: 82538 AN: 151846 Hom.: 22717 Cov.: 31 AF XY: 0.545 AC XY: 40450 AN XY: 74214

African (AFR) AF: 0.462 AC: 19130 AN: 41380

American (AMR) AF: 0.632 AC: 9656 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2043 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3039 AN: 5146

South Asian (SAS) AF: 0.631 AC: 3034 AN: 4808

European-Finnish (FIN) AF: 0.531 AC: 5606 AN: 10560

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38103 AN: 67894

Other (OTH) AF: 0.560 AC: 1181 AN: 2110

Alfa AF: 0.552 Hom.: 35668

Bravo AF: 0.548

Asia WGS AF: 0.612 AC: 2128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.77
PhyloP100		-0.29
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: rs220154; hg19: chr21-43544893;