Genetic Variant UMODL1:c.2104+28C>T (chr21-42111738-C-T) – 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.2104+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,579,198 control chromosomes in the GnomAD database, including 201,737 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 0.43 ( 15308 hom., cov: 33)

Exomes 𝑓: 0.51 ( 186429 hom. )

Consequence

UMODL1
NM_001004416.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302

Publications

9 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3 link	c.2104+28C>T		intron_variant	Intron 12 of 22	ENST00000408910.7	NP_001004416.3	Q5DID0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7 link	c.2104+28C>T		intron_variant	Intron 12 of 22	1	NM_001004416.3	ENSP00000386147.2		Q5DID0-1

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65321

AN:

151958

Hom.:

15316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.482

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.455

GnomAD2 exomes

AF:

0.479

AC:

105189

AN:

219374

AF XY:

0.479

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.485

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.502

GnomAD4 exome

AF:

0.507

AC:

723923

AN:

1427120

Hom.:

186429

Cov.:

AF XY:

0.504

AC XY:

356158

AN XY:

706612

show subpopulations

African (AFR)

AF:

0.213

AC:

7003

AN:

32888

American (AMR)

AF:

0.482

AC:

20618

AN:

42812

Ashkenazi Jewish (ASJ)

AF:

0.477

AC:

11500

AN:

24128

East Asian (EAS)

AF:

0.489

AC:

19164

AN:

39194

South Asian (SAS)

AF:

0.393

AC:

32078

AN:

81672

European-Finnish (FIN)

AF:

0.552

AC:

26727

AN:

48424

Middle Eastern (MID)

AF:

0.430

AC:

2430

AN:

5652

European-Non Finnish (NFE)

AF:

0.527

AC:

575868

AN:

1093274

Other (OTH)

AF:

0.483

AC:

28535

AN:

59076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

19350

38700

58049

77399

96749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16590

33180

49770

66360

82950

<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:

0.430

AC:

65321

AN:

152078

Hom.:

15308

Cov.:

AF XY:

0.430

AC XY:

31961

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.231

AC:

9566

AN:

41480

American (AMR)

AF:

0.450

AC:

6878

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1634

AN:

3468

East Asian (EAS)

AF:

0.485

AC:

2507

AN:

5174

South Asian (SAS)

AF:

0.389

AC:

1876

AN:

4818

European-Finnish (FIN)

AF:

0.563

AC:

5961

AN:

10582

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.521

AC:

35389

AN:

67962

Other (OTH)

AF:

0.451

AC:

950

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1863

3727

5590

7454

9317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.449

Hom.:

3489

Bravo

AF:

0.417

Asia WGS

AF:

0.444

AC:

1547

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

(source)

DANN

Benign

0.57

PhyloP100

0.30

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over