Genetic Variant NM_053274.3:c.1668+19_1668+20delTT (chr1-92247041-GAA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_053274.3(GLMN):c.1668+19_1668+20delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,318,938 control chromosomes in the GnomAD database, including 159,859 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.48 ( 18166 hom., cov: 0)

Exomes 𝑓: 0.48 ( 141693 hom. )

Consequence

GLMN
NM_053274.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.25

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 -10 ACMG points.

BP6

Variant 1-92247041-GAA-G is Benign according to our data. Variant chr1-92247041-GAA-G is described in ClinVar as [Benign]. Clinvar id is 1221423.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-92247041-GAA-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 rank	MANE	Protein	UniProt
GLMN	NM_053274.3 link	c.1668+19_1668+20delTT		intron_variant	Intron 18 of 18	ENST00000370360.8	NP_444504.1	Q92990-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLMN	ENST00000370360.8 link	c.1668+19_1668+20delTT	intron_variant	Intron 18 of 18	1	NM_053274.3	ENSP00000359385.3	Q92990-1
GLMN	ENST00000495106.5 link	n.329+19_329+20delTT	intron_variant	Intron 17 of 17	1		ENSP00000436829.1	Q92990-2
GLMN	ENST00000471465.1 link	n.614+19_614+20delTT	intron_variant	Intron 2 of 2	2
GLMN	ENST00000495852.6 link	c.19_20delTT	downstream_gene_variant		5		ENSP00000469157.2	M0QXG8

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72180

AN:

151640

Hom.:

18155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.617

Gnomad AMR

AF:

0.495

Gnomad ASJ

AF:

0.545

Gnomad EAS

AF:

0.964

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.524

AC:

129637

AN:

247232

Hom.:

37153

AF XY:

0.531

AC XY:

71177

AN XY:

133968

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.968

Gnomad SAS exome

AF:

0.714

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.444

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.476

AC:

555818

AN:

1167180

Hom.:

141693

AF XY:

0.484

AC XY:

288441

AN XY:

595588

show subpopulations

Gnomad4 AFR exome

AF:

0.460

Gnomad4 AMR exome

AF:

0.509

Gnomad4 ASJ exome

AF:

0.528

Gnomad4 EAS exome

AF:

0.962

Gnomad4 SAS exome

AF:

0.706

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.434

Gnomad4 OTH exome

AF:

0.499

GnomAD4 genome

AF:

0.476

AC:

72213

AN:

151758

Hom.:

18166

Cov.:

AF XY:

0.479

AC XY:

35509

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.495

Gnomad4 ASJ

AF:

0.545

Gnomad4 EAS

AF:

0.964

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.442

Gnomad4 OTH

AF:

0.475

Alfa

AF:

0.472

Hom.:

3109

Bravo

AF:

0.482

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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