Genetic Variant UMODL1:c.2105-702A>C (chr21-42112871-A-C) – 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.2105-702A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 150,486 control chromosomes in the GnomAD database, including 17,033 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 0.46 ( 16955 hom., cov: 27)

Exomes 𝑓: 0.54 ( 78 hom. )

Consequence

UMODL1
NM_001004416.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.976

Publications

5 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 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.2105-702A>C	intron	N/A	NP_001004416.3
UMODL1	NM_173568.4		c.2489-702A>C	intron	N/A	NP_775839.4
UMODL1	NM_001199527.3		c.2273-702A>C	intron	N/A	NP_001186456.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.2105-702A>C	intron	N/A	ENSP00000386147.2
UMODL1	ENST00000408989.6	TSL:1	c.2489-702A>C	intron	N/A	ENSP00000386126.2
UMODL1	ENST00000400427.5	TSL:1	c.2273-702A>C	intron	N/A	ENSP00000383279.1

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

69307

AN:

149884

Hom.:

16966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.508

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.524

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.482

GnomAD4 exome

AF:

0.544

AC:

262

AN:

482

Hom.:

AF XY:

0.493

AC XY:

148

AN XY:

300

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.542

AC:

193

AN:

356

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.571

AC:

AN:

Other (OTH)

AF:

0.429

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.462

AC:

69316

AN:

150004

Hom.:

16955

Cov.:

AF XY:

0.463

AC XY:

33909

AN XY:

73216

show subpopulations

African (AFR)

AF:

0.274

AC:

11062

AN:

40426

American (AMR)

AF:

0.508

AC:

7612

AN:

14984

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1791

AN:

3458

East Asian (EAS)

AF:

0.525

AC:

2684

AN:

5116

South Asian (SAS)

AF:

0.475

AC:

2264

AN:

4770

European-Finnish (FIN)

AF:

0.565

AC:

5795

AN:

10250

Middle Eastern (MID)

AF:

0.452

AC:

131

AN:

290

European-Non Finnish (NFE)

AF:

0.539

AC:

36499

AN:

67720

Other (OTH)

AF:

0.480

AC:

1001

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1753

3506

5259

7012

8765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.505

Hom.:

58020

Bravo

AF:

0.448

Asia WGS

AF:

0.491

AC:

1710

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

(source)

DANN

Benign

0.66

PhyloP100

-0.98

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