dbSNP rs2839470: UMODL1:n.280T>C (chr21-42128129-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000484712.1(UMODL1):n.280T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 531,924 control chromosomes in the GnomAD database, including 84,573 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 0.54 ( 22299 hom., cov: 33)

Exomes 𝑓: 0.57 ( 62274 hom. )

Consequence

UMODL1
ENST00000484712.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.68

Publications

10 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=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3 link	c.3690+298T>C		intron_variant	Intron 20 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.3690+298T>C		intron_variant	Intron 20 of 22	1	NM_001004416.3	ENSP00000386147.2		Q5DID0-1

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81743

AN:

152046

Hom.:

22303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.583

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.581

Gnomad OTH

AF:

0.528

GnomAD4 exome

AF:

0.571

AC:

216828

AN:

379758

Hom.:

62274

Cov.:

AF XY:

0.569

AC XY:

120124

AN XY:

210966

show subpopulations

African (AFR)

AF:

0.454

AC:

5217

AN:

11502

American (AMR)

AF:

0.518

AC:

14998

AN:

28960

Ashkenazi Jewish (ASJ)

AF:

0.594

AC:

8297

AN:

13964

East Asian (EAS)

AF:

0.630

AC:

9749

AN:

15472

South Asian (SAS)

AF:

0.526

AC:

31516

AN:

59870

European-Finnish (FIN)

AF:

0.611

AC:

10400

AN:

17012

Middle Eastern (MID)

AF:

0.576

AC:

1824

AN:

3164

European-Non Finnish (NFE)

AF:

0.587

AC:

123415

AN:

210080

Other (OTH)

AF:

0.578

AC:

11412

AN:

19734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

4867

9734

14602

19469

24336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.537

AC:

81775

AN:

152166

Hom.:

22299

Cov.:

AF XY:

0.535

AC XY:

39816

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.458

AC:

18995

AN:

41516

American (AMR)

AF:

0.499

AC:

7625

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.583

AC:

2023

AN:

3470

East Asian (EAS)

AF:

0.606

AC:

3132

AN:

5172

South Asian (SAS)

AF:

0.496

AC:

2395

AN:

4824

European-Finnish (FIN)

AF:

0.603

AC:

6376

AN:

10578

Middle Eastern (MID)

AF:

0.579

AC:

169

AN:

292

European-Non Finnish (NFE)

AF:

0.581

AC:

39485

AN:

68000

Other (OTH)

AF:

0.526

AC:

1113

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1950

3900

5849

7799

9749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.557

Hom.:

46560

Bravo

AF:

0.527

Asia WGS

AF:

0.551

AC:

1918

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.025

(source)

DANN

Benign

0.41

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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