1-92262619-A-G

Variant names:

• chr1-92262619-A-G
• rs10875319
• NM_053274.3:c.1473+244T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_053274.3(GLMN):​c.1473+244T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,100 control chromosomes in the GnomAD database, including 18,310 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (18310 hom., cov: 32)
• Consequence: GLMN NM_053274.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147
• Publications: 4 publications found

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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-92262619-A-G is Benign according to our data. Variant chr1-92262619-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLMN	NM_053274.3	MANE Select	c.1473+244T>C		intron	N/A	NP_444504.1	Q92990-1
	GLMN	NM_001319683.2		c.1431+244T>C		intron	N/A	NP_001306612.1	B4DJ85
	GLMN	NR_135089.2		n.1481+244T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLMN	ENST00000370360.8	TSL:1 MANE Select	c.1473+244T>C		intron	N/A	ENSP00000359385.3	Q92990-1
	GLMN	ENST00000495106.5	TSL:1	n.*134+244T>C		intron	N/A	ENSP00000436829.1	Q92990-2
	GLMN	ENST00000931421.1		c.1473+244T>C		intron	N/A	ENSP00000601480.1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72497 AN: 151982 Hom.: 18298 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.477 AC: 72531 AN: 152100 Hom.: 18310 Cov.: 32 AF XY: 0.480 AC XY: 35684 AN XY: 74356

African (AFR) AF: 0.462 AC: 19167 AN: 41494

American (AMR) AF: 0.496 AC: 7573 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1889 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4998 AN: 5182

South Asian (SAS) AF: 0.716 AC: 3458 AN: 4828

European-Finnish (FIN) AF: 0.345 AC: 3646 AN: 10568

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.443 AC: 30087 AN: 67966

Other (OTH) AF: 0.475 AC: 1003 AN: 2112

Alfa AF: 0.452 Hom.: 12151

Bravo AF: 0.483

Asia WGS AF: 0.801 AC: 2781 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.32
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10875319; hg19: chr1-92728176; COSMIC: COSV64860082; COSMIC: COSV64860082;