X-68829498-C-G

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.-279C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00935 in 372,790 control chromosomes in the GnomAD database, including 21 homozygotes. There are 1,007 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 0.0078 (5 hom., 276 hem., cov: 25)
  • Exomes 𝑓: 0.010 (16 hom. 731 hem.)
• Consequence: EFNB1 NM_004429.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

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=-0.46).
• BP6: Variant X-68829498-C-G is Benign according to our data. Variant chrX-68829498-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1220447.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-68829498-C-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00784 (885/112947) while in subpopulation NFE AF= 0.0116 (618/53194). AF 95% confidence interval is 0.0109. There are 5 homozygotes in gnomad4. There are 276 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFNB1	NM_004429.5	c.-279C>G		5_prime_UTR_variant	1/5	ENST00000204961.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFNB1	ENST00000204961.5	c.-279C>G		5_prime_UTR_variant	1/5	1	NM_004429.5	P1

Frequencies

GnomAD3 genomes AF: 0.00784 AC: 885 AN: 112901 Hom.: 5 Cov.: 25 AF XY: 0.00787 AC XY: 276 AN XY: 35075

Gnomad AFR AF: 0.00148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00828

Gnomad ASJ AF: 0.00189

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.0162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00789

GnomAD4 exome AF: 0.0100 AC: 2600 AN: 259843 Hom.: 16 Cov.: 3 AF XY: 0.00937 AC XY: 731 AN XY: 78017

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00354

Gnomad4 ASJ exome AF: 0.00203

Gnomad4 EAS exome AF: 0.0000614

Gnomad4 SAS exome AF: 0.00368

Gnomad4 FIN exome AF: 0.0206

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.00926

GnomAD4 genome AF: 0.00784 AC: 885 AN: 112947 Hom.: 5 Cov.: 25 AF XY: 0.00786 AC XY: 276 AN XY: 35131

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00827

Gnomad4 ASJ AF: 0.00189

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00437

Gnomad4 FIN AF: 0.0162

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.00779

Alfa AF: 0.00457 Hom.: 24

Bravo AF: 0.00713

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

Nov 13, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	19
Dann	Benign	0.93

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: rs756470369; hg19: chrX-68049341;