rs12703524

Variant names:

• chr7-143408737-C-A
• rs12703524
• NM_005232.5:c.69G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-143408737-C-A
• chr7-143408737-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005232.5(EPHA1):​c.69G>T​(p.Ala23Ala) 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
• Publications: 8 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 -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 VariationId 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.

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.69G>T	p.Ala23Ala	synonymous	Exon 1 of 18	NP_005223.4
	EPHA1-AS1	NR_033897.1		n.74+851C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA1	ENST00000275815.4	TSL:1 MANE Select	c.69G>T	p.Ala23Ala	synonymous	Exon 1 of 18	ENSP00000275815.3	P21709-1
	EPHA1	ENST00000488068.5	TSL:1	n.69G>T		non_coding_transcript_exon	Exon 1 of 16
	EPHA1-AS1	ENST00000429289.5	TSL:1	n.74+851C>A		intron	N/A

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

GnomAD2 exomes AF: 0.500 AC: 1 AN: 2 AF XY: 0.500

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

African (AFR) AF: 0.402 AC: 6926 AN: 17222

American (AMR) AF: 0.370 AC: 2903 AN: 7850

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 5493 AN: 12336

East Asian (EAS) AF: 0.328 AC: 8162 AN: 24904

South Asian (SAS) AF: 0.459 AC: 6555 AN: 14268

European-Finnish (FIN) AF: 0.337 AC: 7037 AN: 20896

Middle Eastern (MID) AF: 0.516 AC: 1220 AN: 2366

European-Non Finnish (NFE) AF: 0.447 AC: 300355 AN: 671998

Other (OTH) AF: 0.438 AC: 15102 AN: 34458

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

African (AFR) AF: 0.376 AC: 14194 AN: 37732

American (AMR) AF: 0.415 AC: 6033 AN: 14528

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1486 AN: 3350

East Asian (EAS) AF: 0.283 AC: 1312 AN: 4640

South Asian (SAS) AF: 0.438 AC: 1865 AN: 4260

European-Finnish (FIN) AF: 0.313 AC: 2998 AN: 9572

Middle Eastern (MID) AF: 0.489 AC: 129 AN: 264

European-Non Finnish (NFE) AF: 0.432 AC: 27985 AN: 64836

Other (OTH) AF: 0.431 AC: 839 AN: 1948

Alfa AF: 0.405 Hom.: 1594

Bravo AF: 0.419

Asia WGS AF: 0.364 AC: 1132 AN: 3116

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
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		0.47
PromoterAI		0.095	Neutral
Mutation Taster		=100/0	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: rs12703524; hg19: chr7-143105830;