1-92262619-A-G

Position:

• chr1-92262619-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLMN	NM_053274.3	c.1473+244T>C		intron_variant		ENST00000370360.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLMN	ENST00000370360.8	c.1473+244T>C		intron_variant		1	NM_053274.3	P1
GLMN	ENST00000495106.5	c.*134+244T>C		intron_variant, NMD_transcript_variant		1
GLMN	ENST00000495852.6	c.696+244T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.475

Alfa AF: 0.457 Hom.: 6990

Bravo AF: 0.483

Asia WGS AF: 0.801 AC: 2781 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.32

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

Other links and lift over

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