rs587777109

Positions:

• chrX-68839753-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP3 PP5

The NM_004429.5(EFNB1):​c.496C>T​(p.Gln166Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 24)
• Consequence: EFNB1 NM_004429.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.87

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant X-68839753-C-T is Pathogenic according to our data. Variant chrX-68839753-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 100627.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-68839753-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNB1	NM_004429.5	c.496C>T	p.Gln166Ter	stop_gained	3/5	ENST00000204961.5	NP_004420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNB1	ENST00000204961.5	c.496C>T	p.Gln166Ter	stop_gained	3/5	1	NM_004429.5	ENSP00000204961	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Craniofrontonasal syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 15, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	45
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.96	D
MutationTaster	Benign	1.0	A
Vest4		0.95
GERP RS		5.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.59		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.59		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777109; hg19: chrX-68059596;