X-68838318-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_004429.5(EFNB1):c.129-299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 111,041 control chromosomes in the GnomAD database, including 4 homozygotes. There are 133 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0043 (4 hom., 133 hem., cov: 23)
• Consequence: EFNB1 NM_004429.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.455

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant X-68838318-C-T is Benign according to our data. Variant chrX-68838318-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1216134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00434 (482/111041) while in subpopulation AFR AF= 0.0147 (450/30579). AF 95% confidence interval is 0.0136. There are 4 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB1	NM_004429.5	c.129-299C>T		intron_variant		ENST00000204961.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB1	ENST00000204961.5	c.129-299C>T		intron_variant		1	NM_004429.5	P1

Frequencies

GnomAD3 genomes AF: 0.00430 AC: 477 AN: 110991 Hom.: 4 Cov.: 23 AF XY: 0.00390 AC XY: 130 AN XY: 33305

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00208

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000947

Gnomad OTH AF: 0.00336

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

GnomAD4 genome AF: 0.00434 AC: 482 AN: 111041 Hom.: 4 Cov.: 23 AF XY: 0.00399 AC XY: 133 AN XY: 33367

Gnomad4 AFR AF: 0.0147

Gnomad4 AMR AF: 0.00208

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000947

Gnomad4 OTH AF: 0.00333

Alfa AF: 0.00463 Hom.: 13

Bravo AF: 0.00524

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	8.3
Dann	Benign	0.84

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: rs142465917; hg19: chrX-68058161;