Variant chr1-92262939-AAT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_053274.3(GLMN):c.1410-15_1410-14del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000901 in 959,728 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00069 ( 2 hom. )

Consequence

GLMN
NM_053274.3 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.52

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 -16 ACMG points.

BP6

Variant 1-92262939-AAT-A is Benign according to our data. Variant chr1-92262939-AAT-A is described in ClinVar as [Likely_benign]. Clinvar id is 298129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00203 (309/152332) while in subpopulation AFR AF= 0.00563 (234/41572). AF 95% confidence interval is 0.00504. There are 1 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 309 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLMN	NM_053274.3 linkuse as main transcript	c.1410-15_1410-14del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000370360.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
GLMN	ENST00000370360.8 linkuse as main transcript	c.1410-15_1410-14del	splice_polypyrimidine_tract_variant, intron_variant	1	NM_053274.3	P1	Q92990-1
GLMN	ENST00000495106.5 linkuse as main transcript	c.71-15_71-14del	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	1			Q92990-2
GLMN	ENST00000463560.1 linkuse as main transcript	c.673-15_673-14del	splice_polypyrimidine_tract_variant, intron_variant	5
GLMN	ENST00000495852.6 linkuse as main transcript	c.633-15_633-14del	splice_polypyrimidine_tract_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

308

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00562

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000852

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000863

AC:

212

AN:

245622

Hom.:

AF XY:

0.000736

AC XY:

AN XY:

133160

show subpopulations

Gnomad AFR exome

AF:

0.00641

Gnomad AMR exome

AF:

0.000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.000804

Gnomad OTH exome

AF:

0.000834

GnomAD4 exome

AF:

0.000689

AC:

556

AN:

807396

Hom.:

AF XY:

0.000588

AC XY:

249

AN XY:

423740

show subpopulations

Gnomad4 AFR exome

AF:

0.00554

Gnomad4 AMR exome

AF:

0.000354

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.0000136

Gnomad4 FIN exome

AF:

0.000241

Gnomad4 NFE exome

AF:

0.000721

Gnomad4 OTH exome

AF:

0.000818

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152332

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00563

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00223

Asia WGS

AF:

0.000868

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glomuvenous malformation

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 16, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.45

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.45

Position offset: -13

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