Variant 1-92246415-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_053274.3(GLMN):c.*115G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 638,150 control chromosomes in the GnomAD database, including 86,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18164 hom., cov: 32)

Exomes 𝑓: 0.51 ( 68042 hom. )

Consequence

GLMN
NM_053274.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0740

Variant links:

Genes affected

GLMN (HGNC:14373): (glomulin, FKBP associated protein) This gene encodes a phosphorylated protein that is a member of a Skp1-Cullin-F-box-like complex. The protein is essential for normal development of the vasculature and mutations in this gene have been associated with glomuvenous malformations, also called glomangiomas. Multiple splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

GLMN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-92246415-C-G is Benign according to our data. Variant chr1-92246415-C-G is described in ClinVar as [Benign]. Clinvar id is 298125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92246415-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLMN	NM_053274.3 linkuse as main transcript	c.*115G>C		3_prime_UTR_variant	19/19	ENST00000370360.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLMN	ENST00000370360.8 linkuse as main transcript	c.*115G>C		3_prime_UTR_variant	19/19	1	NM_053274.3	P1	Q92990-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72133

AN:

151772

Hom.:

18153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.964

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.470

GnomAD4 exome

AF:

0.507

AC:

246556

AN:

486260

Hom.:

68042

Cov.:

AF XY:

0.517

AC XY:

135696

AN XY:

262532

show subpopulations

Gnomad4 AFR exome

AF:

0.468

Gnomad4 AMR exome

AF:

0.511

Gnomad4 ASJ exome

AF:

0.530

Gnomad4 EAS exome

AF:

0.961

Gnomad4 SAS exome

AF:

0.708

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.475

AC:

72164

AN:

151890

Hom.:

18164

Cov.:

AF XY:

0.478

AC XY:

35490

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.454

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.544

Gnomad4 EAS

AF:

0.964

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.444

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.449

Hom.:

1864

Bravo

AF:

0.481

Asia WGS

AF:

0.798

AC:

2754

AN:

3458

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Glomuvenous malformation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.50

DANN

Benign

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over