Genetic Variant GLMN:c.1586-162_1586-161delCT (chr1-92247304-CAG-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_053274.3(GLMN):c.1586-162_1586-161delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,892 control chromosomes in the GnomAD database, including 6,481 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 6481 hom., cov: 23)

Consequence

GLMN
NM_053274.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.421

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

glomuvenous malformation
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

GLMN links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-92247304-CAG-C is Benign according to our data. Variant chr1-92247304-CAG-C is described in ClinVar as Benign. ClinVar VariationId is 1294738.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053274.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLMN	NM_053274.3	MANE Select	c.1586-162_1586-161delCT	intron	N/A	NP_444504.1	Q92990-1
GLMN	NM_001319683.2		c.1544-162_1544-161delCT	intron	N/A	NP_001306612.1	B4DJ85
GLMN	NR_135089.2		n.1594-162_1594-161delCT	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLMN	ENST00000370360.8	TSL:1 MANE Select	c.1586-162_1586-161delCT	intron	N/A	ENSP00000359385.3	Q92990-1
GLMN	ENST00000495106.5	TSL:1	n.247-162_247-161delCT	intron	N/A	ENSP00000436829.1	Q92990-2
GLMN	ENST00000931421.1		c.1652-162_1652-161delCT	intron	N/A	ENSP00000601480.1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39435

AN:

151776

Hom.:

6472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0776

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.308

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.0337

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.352

Gnomad OTH

AF:

0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.260

AC:

39461

AN:

151892

Hom.:

6481

Cov.:

AF XY:

0.261

AC XY:

19390

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.0776

AC:

3219

AN:

41472

American (AMR)

AF:

0.308

AC:

4697

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1179

AN:

3464

East Asian (EAS)

AF:

0.0336

AC:

174

AN:

5182

South Asian (SAS)

AF:

0.223

AC:

1076

AN:

4824

European-Finnish (FIN)

AF:

0.419

AC:

4397

AN:

10488

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.352

AC:

23891

AN:

67890

Other (OTH)

AF:

0.266

AC:

562

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1368

2735

4103

5470

6838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.309

Hom.:

991

Bravo

AF:

0.246

Asia WGS

AF:

0.127

AC:

443

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.42

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over