Genetic Variant ENST00000475047.1:n.414A>G (chr21-42113033-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000475047.1(UMODL1):n.414A>G 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 0.304 in 152,698 control chromosomes in the GnomAD database, including 7,196 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 0.30 ( 7171 hom., cov: 32)

Exomes 𝑓: 0.24 ( 25 hom. )

Consequence

UMODL1
ENST00000475047.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.30

Publications

6 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475047.1. 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.2105-540A>G	intron	N/A	NP_001004416.3
UMODL1	NM_173568.4		c.2489-540A>G	intron	N/A	NP_775839.4
UMODL1	NM_001199527.3		c.2273-540A>G	intron	N/A	NP_001186456.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UMODL1	ENST00000475047.1	TSL:1	n.414A>G	non_coding_transcript_exon	Exon 2 of 4
UMODL1	ENST00000408910.7	TSL:1 MANE Select	c.2105-540A>G	intron	N/A	ENSP00000386147.2
UMODL1	ENST00000408989.6	TSL:1	c.2489-540A>G	intron	N/A	ENSP00000386126.2

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46122

AN:

151868

Hom.:

7155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.283

GnomAD4 exome

AF:

0.237

AC:

169

AN:

712

Hom.:

Cov.:

AF XY:

0.254

AC XY:

103

AN XY:

406

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.143

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.304

AC:

119

AN:

392

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.155

AC:

AN:

278

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.304

AC:

46188

AN:

151986

Hom.:

7171

Cov.:

AF XY:

0.309

AC XY:

22962

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.362

AC:

14977

AN:

41422

American (AMR)

AF:

0.323

AC:

4940

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3472

East Asian (EAS)

AF:

0.337

AC:

1740

AN:

5168

South Asian (SAS)

AF:

0.338

AC:

1629

AN:

4814

European-Finnish (FIN)

AF:

0.302

AC:

3187

AN:

10560

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17809

AN:

67956

Other (OTH)

AF:

0.288

AC:

607

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1612

3223

4835

6446

8058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.276

Hom.:

1270

Bravo

AF:

0.307

Asia WGS

AF:

0.336

AC:

1166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.59

(source)

DANN

Benign

0.49

PhyloP100

-2.3

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