1-92247041-GAAA-GA

Variant names:

• chr1-92247041-GAA-G
• rs35752451
• NM_053274.3:c.1668+19_1668+20delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 1.25
• Publications: 5 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 -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 VariationId is 1221423.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.1668+19_1668+20delTT		intron	N/A	NP_444504.1	Q92990-1
	GLMN	NM_001319683.2		c.1626+19_1626+20delTT		intron	N/A	NP_001306612.1	B4DJ85
	GLMN	NR_135089.2		n.1676+19_1676+20delTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLMN	ENST00000370360.8	TSL:1 MANE Select	c.1668+19_1668+20delTT		intron	N/A	ENSP00000359385.3	Q92990-1
	GLMN	ENST00000495106.5	TSL:1	n.*329+19_*329+20delTT		intron	N/A	ENSP00000436829.1	Q92990-2
	GLMN	ENST00000931421.1		c.1734+19_1734+20delTT		intron	N/A	ENSP00000601480.1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72180 AN: 151640 Hom.: 18155 Cov.: 0

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

GnomAD2 exomes AF: 0.524 AC: 129637 AN: 247232 AF XY: 0.531

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 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

African (AFR) AF: 0.460 AC: 12839 AN: 27936

American (AMR) AF: 0.509 AC: 22564 AN: 44360

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 12846 AN: 24328

East Asian (EAS) AF: 0.962 AC: 36923 AN: 38378

South Asian (SAS) AF: 0.706 AC: 56781 AN: 80412

European-Finnish (FIN) AF: 0.366 AC: 17968 AN: 49134

Middle Eastern (MID) AF: 0.566 AC: 2949 AN: 5214

European-Non Finnish (NFE) AF: 0.434 AC: 367781 AN: 846970

Other (OTH) AF: 0.499 AC: 25167 AN: 50448

GnomAD4 genome AF: 0.476 AC: 72213 AN: 151758 Hom.: 18166 Cov.: 0 AF XY: 0.479 AC XY: 35509 AN XY: 74166

African (AFR) AF: 0.460 AC: 19056 AN: 41384

American (AMR) AF: 0.495 AC: 7534 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1892 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4972 AN: 5158

South Asian (SAS) AF: 0.715 AC: 3430 AN: 4800

European-Finnish (FIN) AF: 0.344 AC: 3620 AN: 10522

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 29993 AN: 67874

Other (OTH) AF: 0.475 AC: 1004 AN: 2114

Alfa AF: 0.472 Hom.: 3109

Bravo AF: 0.482

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
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: rs35752451; hg19: chr1-92712598;