Genetic Variant NM_005232.5:c.2889C>T (chr7-143391499-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005232.5(EPHA1):c.2889C>T(p.His963His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,614,164 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 49 hom. )

Consequence

EPHA1
NM_005232.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

EPHA1 (HGNC:3385): (EPH receptor A1) 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 is expressed in some human cancer cell lines and has been implicated in carcinogenesis. [provided by RefSeq, Jul 2008]

EPHA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 7-143391499-G-A is Benign according to our data. Variant chr7-143391499-G-A is described in ClinVar as [Benign]. Clinvar id is 781115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.84 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1858/152280) while in subpopulation AFR AF= 0.0428 (1778/41560). AF 95% confidence interval is 0.0411. There are 39 homozygotes in gnomad4. There are 862 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPHA1	NM_005232.5 link	c.2889C>T	p.His963His	synonymous_variant	Exon 18 of 18	ENST00000275815.4	NP_005223.4	P21709-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPHA1	ENST00000275815.4 link	c.2889C>T	p.His963His	synonymous_variant	Exon 18 of 18	1	NM_005232.5	ENSP00000275815.3	P21709-1
EPHA1	ENST00000488068.5 link	n.2834C>T		non_coding_transcript_exon_variant	Exon 16 of 16	1
EPHA1	ENST00000458129.1 link	n.-108C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1852

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0428

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

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:

0.000118

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00315

AC:

791

AN:

251358

Hom.:

AF XY:

0.00234

AC XY:

318

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0439

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00129

AC:

1886

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

826

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.0122

AC:

1858

AN:

152280

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

862

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0428

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00528

Hom.:

Bravo

AF:

0.0140

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.0

DANN

Benign

0.88

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