dbSNP rs220285: UMODL1:c.77-97C>G (chr21-42075908-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001004416.3(UMODL1):c.77-97C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,544,070 control chromosomes in the GnomAD database, including 279,276 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 0.57 ( 25114 hom., cov: 35)

Exomes 𝑓: 0.60 ( 254162 hom. )

Consequence

UMODL1
NM_001004416.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004416.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UMODL1	NM_001004416.3	MANE Select	c.77-97C>G	intron	N/A	NP_001004416.3
UMODL1	NM_173568.4		c.77-97C>G	intron	N/A	NP_775839.4
UMODL1	NM_001199527.3		c.-140-97C>G	intron	N/A	NP_001186456.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.77-97C>G	intron	N/A	ENSP00000386147.2
UMODL1	ENST00000408989.6	TSL:1	c.77-97C>G	intron	N/A	ENSP00000386126.2
UMODL1	ENST00000400427.5	TSL:1	c.-140-97C>G	intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86194

AN:

152126

Hom.:

25089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.580

GnomAD4 exome

AF:

0.598

AC:

831694

AN:

1391826

Hom.:

254162

AF XY:

0.595

AC XY:

407905

AN XY:

685608

show subpopulations

African (AFR)

AF:

0.532

AC:

16912

AN:

31806

American (AMR)

AF:

0.465

AC:

19429

AN:

41784

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

13164

AN:

22784

East Asian (EAS)

AF:

0.198

AC:

7750

AN:

39044

South Asian (SAS)

AF:

0.474

AC:

36668

AN:

77322

European-Finnish (FIN)

AF:

0.579

AC:

26527

AN:

45844

Middle Eastern (MID)

AF:

0.583

AC:

2767

AN:

4748

European-Non Finnish (NFE)

AF:

0.630

AC:

675247

AN:

1071000

Other (OTH)

AF:

0.578

AC:

33230

AN:

57494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

16966

33932

50897

67863

84829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18108

36216

54324

72432

90540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.567

AC:

86257

AN:

152244

Hom.:

25114

Cov.:

AF XY:

0.561

AC XY:

41730

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.542

AC:

22494

AN:

41540

American (AMR)

AF:

0.545

AC:

8328

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

1982

AN:

3468

East Asian (EAS)

AF:

0.165

AC:

856

AN:

5174

South Asian (SAS)

AF:

0.451

AC:

2179

AN:

4832

European-Finnish (FIN)

AF:

0.575

AC:

6100

AN:

10602

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.624

AC:

42458

AN:

68014

Other (OTH)

AF:

0.572

AC:

1211

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1958

3915

5873

7830

9788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.596

Hom.:

3412

Bravo

AF:

0.563

Asia WGS

AF:

0.315

AC:

1095

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.034

(source)

DANN

Benign

0.38

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over