rs13047454

Positions:

• chr21-42119813-A-G

Variant summary

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

The NM_001004416.3(UMODL1):​c.2689+489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,128 control chromosomes in the GnomAD database, including 10,911 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 0.38 (10911 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.2689+489A>G		intron_variant		ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.2689+489A>G		intron_variant		1	NM_001004416.3	ENSP00000386147	P2
UMODL1	ENST00000400424.6	c.2473+489A>G		intron_variant		1		ENSP00000383276	A2
UMODL1	ENST00000400427.5	c.2857+489A>G		intron_variant		1		ENSP00000383279	A2
UMODL1	ENST00000408989.6	c.3073+489A>G		intron_variant		1		ENSP00000386126	A2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57139 AN: 152010 Hom.: 10900 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.376 AC: 57193 AN: 152128 Hom.: 10911 Cov.: 33 AF XY: 0.370 AC XY: 27486 AN XY: 74380

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.406

Alfa AF: 0.385 Hom.: 14038

Bravo AF: 0.387

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.32

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: rs13047454; hg19: chr21-43539923;