7-100803321-GTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004444.5(EPHB4):c.*138_*139del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,073,722 control chromosomes in the GnomAD database, including 135 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (54 hom.)
• Consequence: EPHB4 NM_004444.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70

Genes affected

EPHB4 (HGNC:3395): (EPH receptor B4) Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-100803321-GTC-G is Benign according to our data. Variant chr7-100803321-GTC-G is described in ClinVar as [Benign]. Clinvar id is 1282284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPHB4	NM_004444.5	c.*138_*139del		3_prime_UTR_variant	17/17	ENST00000358173.8
EPHB4	XM_017011816.2	c.*138_*139del		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHB4	ENST00000358173.8	c.*138_*139del		3_prime_UTR_variant	17/17	1	NM_004444.5	P1
EPHB4	ENST00000360620.7	c.*138_*139del		3_prime_UTR_variant	16/16	1
EPHB4	ENST00000487222.5	n.4303_4304del		non_coding_transcript_exon_variant	16/16	1
EPHB4	ENST00000616502.4	c.*1567_*1568del		3_prime_UTR_variant	14/14	5

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2744 AN: 152118 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00714

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00179 AC: 1645 AN: 921486 Hom.: 54 AF XY: 0.00163 AC XY: 731 AN XY: 447158

Gnomad4 AFR exome AF: 0.0637

Gnomad4 AMR exome AF: 0.00448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000157

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.00381

GnomAD4 genome AF: 0.0181 AC: 2755 AN: 152236 Hom.: 81 Cov.: 32 AF XY: 0.0177 AC XY: 1320 AN XY: 74422

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.00707

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0158 Hom.: 2

Bravo AF: 0.0208

Asia WGS AF: 0.00751 AC: 26 AN: 3478

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

May 26, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs113576131; hg19: chr7-100400943;