7-143408733-C-G

Variant names:

• chr7-143408733-C-G
• rs1467190935
• NM_005232.5:c.73G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005232.5(EPHA1):​c.73G>C​(p.Ala25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 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. A25S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 26)
  • Exomes 𝑓: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPHA1 NM_005232.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31239694).

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.73G>C	p.Ala25Pro	missense	Exon 1 of 18	NP_005223.4
	EPHA1-AS1	NR_033897.1		n.74+847C>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.73G>C	p.Ala25Pro	missense	Exon 1 of 18	ENSP00000275815.3	P21709-1
	EPHA1	ENST00000488068.5	TSL:1	n.73G>C		non_coding_transcript_exon	Exon 1 of 16
	EPHA1-AS1	ENST00000429289.5	TSL:1	n.74+847C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000672 AC: 1 AN: 148840 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000202 AC: 16 AN: 793034 Hom.: 0 Cov.: 11 AF XY: 0.0000237 AC XY: 9 AN XY: 380230

African (AFR) AF: 0.00 AC: 0 AN: 17028

American (AMR) AF: 0.00 AC: 0 AN: 7846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12302

East Asian (EAS) AF: 0.00 AC: 0 AN: 24824

South Asian (SAS) AF: 0.00 AC: 0 AN: 13958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2342

European-Non Finnish (NFE) AF: 0.0000212 AC: 14 AN: 659782

Other (OTH) AF: 0.0000587 AC: 2 AN: 34070

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000672 AC: 1 AN: 148840 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 72586

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40302

American (AMR) AF: 0.00 AC: 0 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 4956

South Asian (SAS) AF: 0.00 AC: 0 AN: 4644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 66904

Other (OTH) AF: 0.00 AC: 0 AN: 2024

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.25	N
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.74	N
PhyloP100		0.20
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		0.89	P
Vest4		0.33
MutPred		0.38		Gain of disorder (P = 0.0307)
MVP		0.59
MPC		0.17
ClinPred		0.24	T
GERP RS		0.80
PromoterAI		0.021	Neutral
Varity_R		0.091
gMVP		0.60
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1467190935; hg19: chr7-143105826;