rs220149

Positions:

• chr21-42120350-G-T
• chr21-42120350-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(UMODL1):​c.2690-737G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,106 control chromosomes in the GnomAD database, including 24,570 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 0.56 (24570 hom., cov: 34)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.2690-737G>T		intron_variant		ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.2690-737G>T		intron_variant		1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.3074-737G>T		intron_variant		1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.2858-737G>T		intron_variant		1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.2474-737G>T		intron_variant		1		ENSP00000383276.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85657 AN: 151988 Hom.: 24547 Cov.: 34

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.564 AC: 85732 AN: 152106 Hom.: 24570 Cov.: 34 AF XY: 0.561 AC XY: 41688 AN XY: 74354

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.596

Alfa AF: 0.604 Hom.: 37527

Bravo AF: 0.574

Asia WGS AF: 0.575 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.25
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs220149; hg19: chr21-43540460;