chr1-22601179-G-A

Variant names:

• chr1-22601179-G-A
• rs12126436
• NM_020526.5:c.2729+91G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020526.5(EPHA8):​c.2729+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,530,784 control chromosomes in the GnomAD database, including 9,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.091 (809 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8598 hom.)
• Consequence: EPHA8 NM_020526.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 2 publications found

Genes affected

EPHA8 (HGNC:3391): (EPH receptor A8) This gene encodes a member of 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. The protein encoded by this gene functions as a receptor for ephrin A2, A3 and A5 and plays a role in short-range contact-mediated axonal guidance during development of the mammalian nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020526.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA8	NM_020526.5	MANE Select	c.2729+91G>A		intron	N/A	NP_065387.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPHA8	ENST00000166244.8	TSL:2 MANE Select	c.2729+91G>A		intron	N/A	ENSP00000166244.3

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13753 AN: 151968 Hom.: 806 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0966

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.106 AC: 146671 AN: 1378698 Hom.: 8598 Cov.: 31 AF XY: 0.108 AC XY: 73132 AN XY: 679128

African (AFR) AF: 0.0280 AC: 865 AN: 30842

American (AMR) AF: 0.231 AC: 7603 AN: 32844

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 2063 AN: 20886

East Asian (EAS) AF: 0.0198 AC: 773 AN: 39102

South Asian (SAS) AF: 0.149 AC: 10850 AN: 72950

European-Finnish (FIN) AF: 0.0966 AC: 4529 AN: 46906

Middle Eastern (MID) AF: 0.149 AC: 802 AN: 5390

European-Non Finnish (NFE) AF: 0.106 AC: 113364 AN: 1072858

Other (OTH) AF: 0.102 AC: 5822 AN: 56920

GnomAD4 genome AF: 0.0906 AC: 13778 AN: 152086 Hom.: 809 Cov.: 32 AF XY: 0.0931 AC XY: 6921 AN XY: 74320

African (AFR) AF: 0.0319 AC: 1325 AN: 41528

American (AMR) AF: 0.176 AC: 2689 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0966 AC: 335 AN: 3468

East Asian (EAS) AF: 0.0254 AC: 130 AN: 5110

South Asian (SAS) AF: 0.149 AC: 718 AN: 4818

European-Finnish (FIN) AF: 0.0939 AC: 996 AN: 10608

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.107 AC: 7284 AN: 67954

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.0904 Hom.: 112

Bravo AF: 0.0948

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.82
PhyloP100		-0.48
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: rs12126436; hg19: chr1-22927672;