rs220168

Variant names:

• chr21-42134461-A-G
• rs220168
• NM_001004416.3:c.3776-2978A>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.3776-2978A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,962 control chromosomes in the GnomAD database, including 17,595 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 0.48 (17595 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3776-2978A>G		intron_variant	Intron 21 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3776-2978A>G		intron_variant	Intron 21 of 22	1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72258 AN: 151844 Hom.: 17573 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.476 AC: 72324 AN: 151962 Hom.: 17595 Cov.: 32 AF XY: 0.469 AC XY: 34808 AN XY: 74238

African (AFR) AF: 0.484 AC: 20056 AN: 41434

American (AMR) AF: 0.473 AC: 7229 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.245 AC: 1267 AN: 5170

South Asian (SAS) AF: 0.407 AC: 1958 AN: 4808

European-Finnish (FIN) AF: 0.441 AC: 4647 AN: 10540

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.490 AC: 33308 AN: 67954

Other (OTH) AF: 0.458 AC: 965 AN: 2108

Alfa AF: 0.490 Hom.: 36639

Bravo AF: 0.480

Asia WGS AF: 0.337 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.41
PhyloP100		-1.8
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: rs220168; hg19: chr21-43554571;