Variant chr1-16155675-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004431.5(EPHA2):c.85+173G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 481,912 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 1 hom. )

Consequence

EPHA2
NM_004431.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.533

Variant links:

Genes affected

EPHA2 (HGNC:3386): (EPH receptor A2) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin 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. This gene encodes a protein that binds ephrin-A ligands. Mutations in this gene are the cause of certain genetically-related cataract disorders.[provided by RefSeq, May 2010]

EPHA2 links:

EPHA2-AS1 (HGNC:40216): (EPHA2 antisense RNA 1)

EPHA2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-16155675-C-G is Benign according to our data. Variant chr1-16155675-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1216566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00525 (799/152320) while in subpopulation AFR AF= 0.018 (750/41574). AF 95% confidence interval is 0.017. There are 10 homozygotes in gnomad4. There are 359 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 799 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
EPHA2	NM_004431.5 linkuse as main transcript	c.85+173G>C	intron_variant		ENST00000358432.8
EPHA2-AS1	XR_007065487.1 linkuse as main transcript	n.461C>G	non_coding_transcript_exon_variant	1/5
EPHA2	NM_001329090.2 linkuse as main transcript	c.-10+173G>C	intron_variant
EPHA2	XM_017000537.2 linkuse as main transcript	c.85+173G>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPHA2	ENST00000358432.8 linkuse as main transcript	c.85+173G>C	intron_variant		1	NM_004431.5	P1	P29317-1
EPHA2-AS1	ENST00000424774.2 linkuse as main transcript	n.500C>G	non_coding_transcript_exon_variant	1/2	2
EPHA2	ENST00000461614.1 linkuse as main transcript	n.205+173G>C	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

797

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00334

GnomAD4 exome

AF:

0.000613

AC:

202

AN:

329592

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

AN XY:

170118

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.00220

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000440

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000183

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00525

AC:

799

AN:

152320

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00611

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over