7-100824547-T-G

Variant names:

• chr7-100824547-T-G
• rs314310
• NM_004444.5:c.53-274A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004444.5(EPHB4):​c.53-274A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 443,646 control chromosomes in the GnomAD database, including 85,489 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27403 hom., cov: 33)
  • Exomes 𝑓: 0.63 (58086 hom.)
• Consequence: EPHB4 NM_004444.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHB4	NM_004444.5	c.53-274A>C		intron_variant	Intron 1 of 16	ENST00000358173.8	NP_004435.3
EPHB4	XM_017011816.2	c.53-274A>C		intron_variant	Intron 1 of 16		XP_016867305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPHB4	ENST00000358173.8	c.53-274A>C		intron_variant	Intron 1 of 16	1	NM_004444.5	ENSP00000350896.3

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90831 AN: 151908 Hom.: 27394 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.629 AC: 183364 AN: 291620 Hom.: 58086 Cov.: 2 AF XY: 0.631 AC XY: 96541 AN XY: 152960

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.601

Gnomad4 EAS exome AF: 0.674

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.621

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.598 AC: 90873 AN: 152026 Hom.: 27403 Cov.: 33 AF XY: 0.603 AC XY: 44792 AN XY: 74320

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.633

Alfa AF: 0.601 Hom.: 4059

Bravo AF: 0.600

Asia WGS AF: 0.585 AC: 2039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.31
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs314310; hg19: chr7-100422169;