rs71586740

Variant names:

• chr1-92247304-CAG-C
• rs71586740
• NM_053274.3:c.1586-162_1586-161delCT

Your query was ambiguous. Multiple possible variants found:

• chr1-92247304-CAG-C
• chr1-92247304-CAG-CAGAG

Variant summary

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

The NM_053274.3(GLMN):​c.1586-162_1586-161delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,892 control chromosomes in the GnomAD database, including 6,481 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6481 hom., cov: 23)
• Consequence: GLMN NM_053274.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.421
• Publications: 0 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: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 1-92247304-CAG-C is Benign according to our data. Variant chr1-92247304-CAG-C is described in ClinVar as Benign. ClinVar VariationId is 1294738.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 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.1586-162_1586-161delCT		intron	N/A	NP_444504.1	Q92990-1
	GLMN	NM_001319683.2		c.1544-162_1544-161delCT		intron	N/A	NP_001306612.1	B4DJ85
	GLMN	NR_135089.2		n.1594-162_1594-161delCT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLMN	ENST00000370360.8	TSL:1 MANE Select	c.1586-162_1586-161delCT		intron	N/A	ENSP00000359385.3	Q92990-1
	GLMN	ENST00000495106.5	TSL:1	n.*247-162_*247-161delCT		intron	N/A	ENSP00000436829.1	Q92990-2
	GLMN	ENST00000931421.1		c.1652-162_1652-161delCT		intron	N/A	ENSP00000601480.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39435 AN: 151776 Hom.: 6472 Cov.: 23

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.260 AC: 39461 AN: 151892 Hom.: 6481 Cov.: 23 AF XY: 0.261 AC XY: 19390 AN XY: 74208

African (AFR) AF: 0.0776 AC: 3219 AN: 41472

American (AMR) AF: 0.308 AC: 4697 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3464

East Asian (EAS) AF: 0.0336 AC: 174 AN: 5182

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4824

European-Finnish (FIN) AF: 0.419 AC: 4397 AN: 10488

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23891 AN: 67890

Other (OTH) AF: 0.266 AC: 562 AN: 2116

Alfa AF: 0.309 Hom.: 991

Bravo AF: 0.246

Asia WGS AF: 0.127 AC: 443 AN: 3474

ClinVar

ClinVar submissions

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
PhyloP100		0.42
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: rs71586740; hg19: chr1-92712861;