dbSNP rs1475911: UMODL1:c.931+2932A>C (chr21-42093370-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.931+2932A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 153,100 control chromosomes in the GnomAD database, including 3,362 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 0.20 ( 3347 hom., cov: 32)

Exomes 𝑓: 0.15 ( 15 hom. )

Consequence

UMODL1
NM_001004416.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.375

Publications

7 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:

Genome browser will be placed here

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 (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UMODL1	NM_001004416.3 link	c.931+2932A>C		intron_variant	Intron 6 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.931+2932A>C		intron_variant	Intron 6 of 22	1	NM_001004416.3	ENSP00000386147.2		Q5DID0-1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30146

AN:

151878

Hom.:

3345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.153

AC:

169

AN:

1104

Hom.:

Cov.:

AF XY:

0.155

AC XY:

AN XY:

594

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.203

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

AN:

East Asian (EAS)

AF:

0.125

AC:

AN:

South Asian (SAS)

AF:

0.184

AC:

AN:

European-Finnish (FIN)

AF:

0.0385

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.145

AC:

116

AN:

802

Other (OTH)

AF:

0.218

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.198

AC:

30160

AN:

151996

Hom.:

3347

Cov.:

AF XY:

0.206

AC XY:

15274

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.121

AC:

5005

AN:

41470

American (AMR)

AF:

0.254

AC:

3883

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

588

AN:

3470

East Asian (EAS)

AF:

0.368

AC:

1894

AN:

5140

South Asian (SAS)

AF:

0.333

AC:

1602

AN:

4814

European-Finnish (FIN)

AF:

0.259

AC:

2734

AN:

10574

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13737

AN:

67950

Other (OTH)

AF:

0.183

AC:

385

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1211

2422

3632

4843

6054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.192

Hom.:

380

Bravo

AF:

0.194

Asia WGS

AF:

0.342

AC:

1192

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.1

(source)

DANN

Benign

0.77

PhyloP100

-0.38

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