X-68829392-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004429.5(EFNB1):c.-385G>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 0.0119 in 216,004 control chromosomes in the GnomAD database, including 75 homozygotes. There are 669 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (73 hom., 646 hem., cov: 24)
  • Exomes 𝑓: 0.0011 (2 hom. 23 hem.)
• Consequence: EFNB1 NM_004429.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

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=-0.77).
• BP6: Variant X-68829392-G-T is Benign according to our data. Variant chrX-68829392-G-T is described in ClinVar as [Benign]. Clinvar id is 1277903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB1	NM_004429.5	c.-385G>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.-385G>T		5_prime_UTR_variant	1/5	1	NM_004429.5	P1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 2463 AN: 112038 Hom.: 73 Cov.: 24 AF XY: 0.0188 AC XY: 645 AN XY: 34256

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00621

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000767

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000302

Gnomad OTH AF: 0.0132

GnomAD4 exome AF: 0.00109 AC: 113 AN: 103918 Hom.: 2 Cov.: 0 AF XY: 0.000760 AC XY: 23 AN XY: 30266

Gnomad4 AFR exome AF: 0.0636

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000214

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.00290

GnomAD4 genome AF: 0.0220 AC: 2465 AN: 112086 Hom.: 73 Cov.: 24 AF XY: 0.0188 AC XY: 646 AN XY: 34314

Gnomad4 AFR AF: 0.0765

Gnomad4 AMR AF: 0.00620

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000770

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000302

Gnomad4 OTH AF: 0.0131

Alfa AF: 0.0182 Hom.: 61

Bravo AF: 0.0253

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Benign	0.94

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: rs187341605; hg19: chrX-68049235;