NM_004440.4:c.2076G>A

Variant names:

• chr6-93258133-C-T
• rs345730
• NM_004440.4:c.2076G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004440.4(EPHA7):​c.2076G>A​(p.Pro692Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 1,612,476 control chromosomes in the GnomAD database, including 413,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36230 hom., cov: 30)
  • Exomes 𝑓: 0.72 (377110 hom.)
• Consequence: EPHA7 NM_004440.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240
• Publications: 22 publications found

Genes affected

EPHA7 (HGNC:3390): (EPH receptor A7) 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. Increased expression of this gene is associated with multiple forms of carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 6-93258133-C-T is Benign according to our data. Variant chr6-93258133-C-T is described in ClinVar as Benign. ClinVar VariationId is 1331194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.024 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004440.4. 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
	EPHA7	NM_004440.4	MANE Select	c.2076G>A	p.Pro692Pro	synonymous	Exon 11 of 17	NP_004431.1	Q15375-1
	EPHA7	NM_001376465.1		c.2064G>A	p.Pro688Pro	synonymous	Exon 11 of 17	NP_001363394.1	Q15375-4
	EPHA7	NM_001288629.2		c.2061G>A	p.Pro687Pro	synonymous	Exon 11 of 17	NP_001275558.1	Q15375-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA7	ENST00000369303.9	TSL:1 MANE Select	c.2076G>A	p.Pro692Pro	synonymous	Exon 11 of 17	ENSP00000358309.4	Q15375-1
	EPHA7	ENST00000922908.1		c.2070G>A	p.Pro690Pro	synonymous	Exon 11 of 17	ENSP00000592967.1
	EPHA7	ENST00000680224.1		c.2064G>A	p.Pro688Pro	synonymous	Exon 11 of 17	ENSP00000506130.1	Q15375-4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104407 AN: 151704 Hom.: 36213 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.699

GnomAD2 exomes AF: 0.720 AC: 180801 AN: 250988 AF XY: 0.728

Gnomad AFR exome AF: 0.599

Gnomad AMR exome AF: 0.681

Gnomad ASJ exome AF: 0.739

Gnomad EAS exome AF: 0.803

Gnomad FIN exome AF: 0.705

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.717 AC: 1047550 AN: 1460652 Hom.: 377110 Cov.: 49 AF XY: 0.722 AC XY: 524276 AN XY: 726632

African (AFR) AF: 0.590 AC: 19726 AN: 33418

American (AMR) AF: 0.685 AC: 30599 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 19383 AN: 26106

East Asian (EAS) AF: 0.838 AC: 33227 AN: 39660

South Asian (SAS) AF: 0.837 AC: 72080 AN: 86128

European-Finnish (FIN) AF: 0.705 AC: 37645 AN: 53372

Middle Eastern (MID) AF: 0.773 AC: 4455 AN: 5764

European-Non Finnish (NFE) AF: 0.708 AC: 786616 AN: 1111200

Other (OTH) AF: 0.726 AC: 43819 AN: 60348

GnomAD4 genome AF: 0.688 AC: 104465 AN: 151824 Hom.: 36230 Cov.: 30 AF XY: 0.697 AC XY: 51698 AN XY: 74218

African (AFR) AF: 0.607 AC: 25136 AN: 41402

American (AMR) AF: 0.711 AC: 10797 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2513 AN: 3468

East Asian (EAS) AF: 0.809 AC: 4149 AN: 5128

South Asian (SAS) AF: 0.834 AC: 4024 AN: 4824

European-Finnish (FIN) AF: 0.722 AC: 7636 AN: 10574

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47923 AN: 67918

Other (OTH) AF: 0.701 AC: 1481 AN: 2112

Alfa AF: 0.697 Hom.: 29605

Bravo AF: 0.678

Asia WGS AF: 0.803 AC: 2791 AN: 3478

EpiCase AF: 0.721

EpiControl AF: 0.719

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		-0.024
Mutation Taster		=98/2	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: rs345730; hg19: chr6-93967851;