chr7-143408735-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005232.5(EPHA1):​c.71G>A​(p.Arg24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 948,062 control chromosomes in the GnomAD database, including 1,638 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (292 hom., cov: 26)
  • Exomes 𝑓: 0.021 (1346 hom.)
• Consequence: EPHA1 NM_005232.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016715527).
• BP6: Variant 7-143408735-C-T is Benign according to our data. Variant chr7-143408735-C-T is described in ClinVar as Benign. ClinVar VariationId is 771418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

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>A	p.Arg24His	missense	Exon 1 of 18	NP_005223.4
	EPHA1-AS1	NR_033897.1		n.74+849C>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.71G>A	p.Arg24His	missense	Exon 1 of 18	ENSP00000275815.3	P21709-1
	EPHA1	ENST00000488068.5	TSL:1	n.71G>A		non_coding_transcript_exon	Exon 1 of 16
	EPHA1-AS1	ENST00000429289.5	TSL:1	n.74+849C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 3972 AN: 147856 Hom.: 290 Cov.: 26

Gnomad AFR AF: 0.00383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.00672

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.00933

Gnomad OTH AF: 0.0310

GnomAD2 exomes AF: 0.00 AC: 0 AN: 2 AF XY: 0.00

Gnomad NFE exome AF: 0.00

GnomAD4 exome AF: 0.0214 AC: 17160 AN: 800100 Hom.: 1346 Cov.: 11 AF XY: 0.0213 AC XY: 8170 AN XY: 383330

African (AFR) AF: 0.00429 AC: 74 AN: 17240

American (AMR) AF: 0.104 AC: 818 AN: 7842

Ashkenazi Jewish (ASJ) AF: 0.00707 AC: 87 AN: 12298

East Asian (EAS) AF: 0.303 AC: 7515 AN: 24842

South Asian (SAS) AF: 0.0469 AC: 662 AN: 14116

European-Finnish (FIN) AF: 0.0136 AC: 285 AN: 20904

Middle Eastern (MID) AF: 0.0294 AC: 69 AN: 2348

European-Non Finnish (NFE) AF: 0.00985 AC: 6564 AN: 666194

Other (OTH) AF: 0.0316 AC: 1086 AN: 34316

GnomAD4 genome AF: 0.0269 AC: 3980 AN: 147962 Hom.: 292 Cov.: 26 AF XY: 0.0307 AC XY: 2217 AN XY: 72104

African (AFR) AF: 0.00382 AC: 154 AN: 40344

American (AMR) AF: 0.105 AC: 1557 AN: 14862

Ashkenazi Jewish (ASJ) AF: 0.00672 AC: 23 AN: 3424

East Asian (EAS) AF: 0.257 AC: 1187 AN: 4618

South Asian (SAS) AF: 0.0471 AC: 215 AN: 4562

European-Finnish (FIN) AF: 0.0150 AC: 153 AN: 10190

Middle Eastern (MID) AF: 0.0216 AC: 6 AN: 278

European-Non Finnish (NFE) AF: 0.00932 AC: 622 AN: 66752

Other (OTH) AF: 0.0307 AC: 63 AN: 2052

Alfa AF: 0.0139 Hom.: 12

Bravo AF: 0.0370

ExAC AF: 0.00699 AC: 12

Asia WGS AF: 0.120 AC: 374 AN: 3124

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.020
FATHMM_MKL	Benign	0.19	N
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.45
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.17
Sift	Benign	0.15	T
Sift4G	Benign	0.14	T
Polyphen		0.98	D
Vest4		0.15
MVP		0.76
MPC		0.17
ClinPred		0.41	T
GERP RS		2.8
PromoterAI		0.11	Neutral
Varity_R		0.050
gMVP		0.22
Mutation Taster		=93/7	polymorphism (auto)

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;