NM_005232.5:c.71G>C

Variant names:

• chr7-143408735-C-G
• rs79587607
• NM_005232.5:c.71G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005232.5(EPHA1):​c.71G>C​(p.Arg24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R24H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: EPHA1 NM_005232.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110049725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA1	NM_005232.5	MANE Select	c.71G>C	p.Arg24Pro	missense	Exon 1 of 18	NP_005223.4
	EPHA1-AS1	NR_033897.1		n.74+849C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA1	ENST00000275815.4	TSL:1 MANE Select	c.71G>C	p.Arg24Pro	missense	Exon 1 of 18	ENSP00000275815.3	P21709-1
	EPHA1	ENST00000488068.5	TSL:1	n.71G>C		non_coding_transcript_exon	Exon 1 of 16
	EPHA1-AS1	ENST00000429289.5	TSL:1	n.74+849C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.78
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.17	N
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.45
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	1.0	N
REVEL	Benign	0.14
Sift	Benign	0.51	T
Sift4G	Benign	0.34	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.40		Gain of glycosylation at R24 (P = 0.0245)
MVP		0.58
MPC		0.20
ClinPred		0.23	T
GERP RS		2.8
PromoterAI		0.14	Neutral
Varity_R		0.15
gMVP		0.36
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs79587607; hg19: chr7-143105828;