rs13047454

Variant names:

• chr21-42119813-A-G
• rs13047454
• NM_001004416.3:c.2689+489A>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.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
• Publications: 2 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=-0.93).
• 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 rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.2689+489A>G		intron_variant	Intron 15 of 22	ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.2689+489A>G		intron_variant	Intron 15 of 22	1	NM_001004416.3	ENSP00000386147.2
UMODL1	ENST00000408989.6	c.3073+489A>G		intron_variant	Intron 14 of 21	1		ENSP00000386126.2
UMODL1	ENST00000400427.5	c.2857+489A>G		intron_variant	Intron 14 of 21	1		ENSP00000383279.1
UMODL1	ENST00000400424.6	c.2473+489A>G		intron_variant	Intron 15 of 22	1		ENSP00000383276.1

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

African (AFR) AF: 0.413 AC: 17140 AN: 41466

American (AMR) AF: 0.379 AC: 5798 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1545 AN: 5192

South Asian (SAS) AF: 0.354 AC: 1706 AN: 4824

European-Finnish (FIN) AF: 0.255 AC: 2695 AN: 10586

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25618 AN: 67982

Other (OTH) AF: 0.406 AC: 858 AN: 2112

Alfa AF: 0.379 Hom.: 34798

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
PhyloP100		-0.76
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: rs13047454; hg19: chr21-43539923;