7-143408747-G-T

Variant names:

• chr7-143408747-G-T
• rs1462823087
• NM_005232.5:c.59C>A

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.59C>A​(p.Pro20His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 899,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: EPHA1 NM_005232.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.432
• Publications: 0 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=0.17202312).

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.59C>A	p.Pro20His	missense	Exon 1 of 18	NP_005223.4
	EPHA1-AS1	NR_033897.1		n.74+861G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA1	ENST00000275815.4	TSL:1 MANE Select	c.59C>A	p.Pro20His	missense	Exon 1 of 18	ENSP00000275815.3	P21709-1
	EPHA1	ENST00000488068.5	TSL:1	n.59C>A		non_coding_transcript_exon	Exon 1 of 16
	EPHA1-AS1	ENST00000429289.5	TSL:1	n.74+861G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000333 AC: 3 AN: 899938 Hom.: 0 Cov.: 13 AF XY: 0.00000466 AC XY: 2 AN XY: 429178

African (AFR) AF: 0.00 AC: 0 AN: 19142

American (AMR) AF: 0.00 AC: 0 AN: 8052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13094

East Asian (EAS) AF: 0.0000392 AC: 1 AN: 25502

South Asian (SAS) AF: 0.00 AC: 0 AN: 16146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20988

Middle Eastern (MID) AF: 0.000389 AC: 1 AN: 2570

European-Non Finnish (NFE) AF: 0.00000132 AC: 1 AN: 756814

Other (OTH) AF: 0.00 AC: 0 AN: 37630

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.19	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.43
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.084
Sift	Benign	0.57	T
Sift4G	Benign	0.56	T
Polyphen		0.70	P
Vest4		0.27
MutPred		0.35		Loss of catalytic residue at P20 (P = 0.0216)
MVP		0.73
MPC		0.15
ClinPred		0.18	T
GERP RS		1.8
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.082
gMVP		0.32
Mutation Taster		=84/16	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: rs1462823087; hg19: chr7-143105840;