rs879255545

Variant names:

• chrX-68829868-ACCTGGAGCCCGTAT-A
• rs879255545
• NM_004429.5:c.101_114delCCGTATCCTGGAGC

Your query was ambiguous. Multiple possible variants found:

• chrX-68829868-ACCTGGAGCCCGTAT-A
• chrX-68829868-ACCTGGAGCCCGTAT-ACCTGGAGCCCGTATCCTGGAGCCCGTAT

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1 PP5_Very_Strong

The NM_004429.5(EFNB1):​c.101_114delCCGTATCCTGGAGC​(p.Pro34LeufsTer36) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 24)
• Consequence: EFNB1 NM_004429.5 frameshift
• Clinical Significance: Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

Genes affected

EFNB1 (HGNC:3226): (ephrin B1) The protein encoded by this gene is a type I membrane protein and a ligand of Eph-related receptor tyrosine kinases. It may play a role in cell adhesion and function in the development or maintenance of the nervous system. [provided by RefSeq, Jul 2008]

EFNB1 Gene-Disease associations (from GenCC):

• craniofrontonasal syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Pathogenic. The variant received 16 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant X-68829868-ACCTGGAGCCCGTAT-A is Pathogenic according to our data. Variant chrX-68829868-ACCTGGAGCCCGTAT-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 2500937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004429.5. 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
	EFNB1	NM_004429.5	MANE Select	c.101_114delCCGTATCCTGGAGC	p.Pro34LeufsTer36	frameshift	Exon 1 of 5	NP_004420.1	P98172

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNB1	ENST00000204961.5	TSL:1 MANE Select	c.101_114delCCGTATCCTGGAGC	p.Pro34LeufsTer36	frameshift	Exon 1 of 5	ENSP00000204961.4	P98172
	EFNB1	ENST00000851101.1		c.101_114delCCGTATCCTGGAGC	p.Pro34LeufsTer36	frameshift	Exon 1 of 4	ENSP00000521160.1

Frequencies

GnomAD3 genomes Cov.: 24

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

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Pathogenic/Likely pathogenic

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
2	-	-	Craniofrontonasal syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs879255545; hg19: chrX-68049711;