rs220271

Variant names:

• chr21-42070144-C-T
• rs220271
• ENST00000400427.5:c.-140-5861C>T

Variant summary

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

The ENST00000400427.5(UMODL1):​c.-140-5861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,090 control chromosomes in the GnomAD database, including 44,933 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 0.76 (44933 hom., cov: 33)
• Consequence: UMODL1 ENST00000400427.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001199527.3	c.-140-5861C>T		intron_variant	Intron 1 of 21		NP_001186456.2
UMODL1	NM_001199528.4	c.-140-5861C>T		intron_variant	Intron 1 of 22		NP_001186457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000400427.5	c.-140-5861C>T		intron_variant	Intron 1 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.-140-5861C>T		intron_variant	Intron 1 of 22	1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116146 AN: 151972 Hom.: 44910 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.764 AC: 116209 AN: 152090 Hom.: 44933 Cov.: 33 AF XY: 0.759 AC XY: 56451 AN XY: 74350

African (AFR) AF: 0.718 AC: 29765 AN: 41452

American (AMR) AF: 0.838 AC: 12813 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2605 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2182 AN: 5176

South Asian (SAS) AF: 0.658 AC: 3167 AN: 4816

European-Finnish (FIN) AF: 0.742 AC: 7849 AN: 10576

Middle Eastern (MID) AF: 0.798 AC: 233 AN: 292

European-Non Finnish (NFE) AF: 0.813 AC: 55277 AN: 67996

Other (OTH) AF: 0.779 AC: 1645 AN: 2112

Alfa AF: 0.801 Hom.: 81974

Bravo AF: 0.769

Asia WGS AF: 0.550 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.33
DANN	Benign	0.80
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs220271; hg19: chr21-43490253;