X-68829082-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004429.5(EFNB1):c.-695C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 115,036 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 171 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 0.0048 (0 hom., 169 hem., cov: 25)
  • Exomes 𝑓: 0.0029 (0 hom. 2 hem.)
• Consequence: EFNB1 NM_004429.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.173

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant X-68829082-C-T is Benign according to our data. Variant chrX-68829082-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1723074.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-68829082-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00482 (545/112969) while in subpopulation NFE AF= 0.00715 (381/53265). AF 95% confidence interval is 0.00656. There are 0 homozygotes in gnomad4. There are 169 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 169 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB1	NM_004429.5	c.-695C>T		5_prime_UTR_variant	1/5	ENST00000204961.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB1	ENST00000204961.5	c.-695C>T		5_prime_UTR_variant	1/5	1	NM_004429.5	P1

Frequencies

GnomAD3 genomes AF: 0.00483 AC: 545 AN: 112918 Hom.: 0 Cov.: 25 AF XY: 0.00482 AC XY: 169 AN XY: 35060

Gnomad AFR AF: 0.000932

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00351

Gnomad ASJ AF: 0.00377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.00715

Gnomad OTH AF: 0.00329

GnomAD4 exome AF: 0.00290 AC: 6 AN: 2067 Hom.: 0 Cov.: 0 AF XY: 0.00601 AC XY: 2 AN XY: 333

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00355

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00482 AC: 545 AN: 112969 Hom.: 0 Cov.: 25 AF XY: 0.00481 AC XY: 169 AN XY: 35121

Gnomad4 AFR AF: 0.000930

Gnomad4 AMR AF: 0.00350

Gnomad4 ASJ AF: 0.00377

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00109

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.00715

Gnomad4 OTH AF: 0.00325

Alfa AF: 0.00184 Hom.: 10

Bravo AF: 0.00432

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

Dec 12, 2020

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	13
Dann	Benign	0.95

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: rs189750013; hg19: chrX-68048925;