7-143408737-C-A

Position:

• chr7-143408737-C-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005232.5(EPHA1):​c.69G>T​(p.Ala23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (11971 hom., cov: 20)
  • Exomes 𝑓: 0.44 (79115 hom.)
• Consequence: EPHA1 NM_005232.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.469

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-AS1 (HGNC:27799): (EPHA1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 7-143408737-C-A is Benign according to our data. Variant chr7-143408737-C-A is described in ClinVar as [Benign]. Clinvar id is 768216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.469 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPHA1	NM_005232.5	c.69G>T	p.Ala23=	synonymous_variant	1/18	ENST00000275815.4	NP_005223.4
EPHA1-AS1	NR_033897.1	n.74+851C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPHA1	ENST00000275815.4	c.69G>T	p.Ala23=	synonymous_variant	1/18	1	NM_005232.5	ENSP00000275815	P1
EPHA1-AS1	ENST00000429289.5	n.74+851C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 57154 AN: 141856 Hom.: 11967 Cov.: 20

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.486

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.435

GnomAD3 exomes AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad NFE exome AF: 0.500

GnomAD4 exome AF: 0.439 AC: 353753 AN: 806298 Hom.: 79115 Cov.: 11 AF XY: 0.439 AC XY: 169745 AN XY: 386494

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.403 AC: 57176 AN: 141966 Hom.: 11971 Cov.: 20 AF XY: 0.397 AC XY: 27381 AN XY: 68954

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.431

Alfa AF: 0.405 Hom.: 1594

Bravo AF: 0.419

Asia WGS AF: 0.364 AC: 1132 AN: 3116

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
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: rs12703524; hg19: chr7-143105830;