dbSNP rs12627387: UMODL1:c.-538G>A (chr21-42062817-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000400427.5(UMODL1):c.-538G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,256 control chromosomes in the GnomAD database, including 6,908 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 0.28 ( 6903 hom., cov: 33)

Exomes 𝑓: 0.22 ( 5 hom. )

Consequence

UMODL1
ENST00000400427.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

4 publications found

Variant links:

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]

UMODL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001199527.3 link	c.-538G>A		upstream_gene_variant			NP_001186456.2
UMODL1	NM_001199528.4 link	c.-538G>A		upstream_gene_variant			NP_001186457.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000400427.5 link	c.-538G>A		upstream_gene_variant		1		ENSP00000383279.1
UMODL1	ENST00000400424.6 link	c.-538G>A		upstream_gene_variant		1		ENSP00000383276.1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

41813

AN:

151988

Hom.:

6878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.270

GnomAD4 exome

AF:

0.220

AC:

AN:

150

Hom.:

AF XY:

0.190

AC XY:

AN XY:

126

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.333

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.400

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.194

AC:

AN:

108

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.275

AC:

41897

AN:

152106

Hom.:

6903

Cov.:

AF XY:

0.276

AC XY:

20548

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.457

AC:

18934

AN:

41470

American (AMR)

AF:

0.227

AC:

3474

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

684

AN:

3472

East Asian (EAS)

AF:

0.452

AC:

2335

AN:

5166

South Asian (SAS)

AF:

0.257

AC:

1239

AN:

4816

European-Finnish (FIN)

AF:

0.185

AC:

1965

AN:

10598

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12408

AN:

67988

Other (OTH)

AF:

0.272

AC:

573

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1467

2934

4400

5867

7334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.196

Hom.:

1527

Bravo

AF:

0.291

Asia WGS

AF:

0.347

AC:

1206

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

1.0

(source)

DANN

Benign

0.44

PhyloP100

-1.2

PromoterAI

-0.13

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over