rs220299

Positions:

• chr21-42082652-C-T
• chr21-42082652-C-G

Variant summary

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

The NM_001004416.3(UMODL1):​c.320-1432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,964 control chromosomes in the GnomAD database, including 26,857 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 0.58 (26857 hom., cov: 32)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.320-1432C>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.320-1432C>T		intron_variant		1	NM_001004416.3	ENSP00000386147	P2
UMODL1	ENST00000400424.6	c.104-1432C>T		intron_variant		1		ENSP00000383276	A2
UMODL1	ENST00000400427.5	c.104-1432C>T		intron_variant		1		ENSP00000383279	A2
UMODL1	ENST00000408989.6	c.320-1432C>T		intron_variant		1		ENSP00000386126	A2

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88186 AN: 151846 Hom.: 26848 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.581 AC: 88229 AN: 151964 Hom.: 26857 Cov.: 32 AF XY: 0.582 AC XY: 43198 AN XY: 74250

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.596

Alfa AF: 0.645 Hom.: 30455

Bravo AF: 0.571

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.69
DANN	Benign	0.27

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: rs220299; hg19: chr21-43502762; COSMIC: COSV68555313; COSMIC: COSV68555313;