NM_004428.3:c.*154G>A

Variant names:

• chr1-155134221-G-A
• rs12904
• NM_004428.3:c.*154G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004428.3(EFNA1):​c.*154G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 726,084 control chromosomes in the GnomAD database, including 75,397 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 0.41 (13785 hom., cov: 31)
  • Exomes 𝑓: 0.45 (61612 hom.)
• Consequence: EFNA1 NM_004428.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 69 publications found

Genes affected

EFNA1 (HGNC:3221): (ephrin A1) This gene encodes a member of the ephrin (EPH) family. The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been implicated in mediating developmental events, especially in the nervous system and in erythropoiesis. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. This gene encodes an EFNA class ephrin which binds to the EPHA2, EPHA4, EPHA5, EPHA6, and EPHA7 receptors. Two transcript variants that encode different isoforms were identified through sequence analysis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004428.3. 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
	EFNA1	NM_004428.3	MANE Select	c.*154G>A		3_prime_UTR	Exon 5 of 5	NP_004419.2
	EFNA1	NM_182685.2		c.*154G>A		3_prime_UTR	Exon 4 of 4	NP_872626.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNA1	ENST00000368407.8	TSL:1 MANE Select	c.*154G>A		3_prime_UTR	Exon 5 of 5	ENSP00000357392.3
	EFNA1	ENST00000368406.2	TSL:1	c.*154G>A		3_prime_UTR	Exon 4 of 4	ENSP00000357391.2
	EFNA1	ENST00000469878.5	TSL:3	n.1023G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62454 AN: 151828 Hom.: 13782 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.447 AC: 256580 AN: 574138 Hom.: 61612 Cov.: 7 AF XY: 0.448 AC XY: 134725 AN XY: 300834

African (AFR) AF: 0.313 AC: 4841 AN: 15454

American (AMR) AF: 0.597 AC: 15187 AN: 25426

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 5821 AN: 15604

East Asian (EAS) AF: 0.866 AC: 27647 AN: 31914

South Asian (SAS) AF: 0.482 AC: 25148 AN: 52134

European-Finnish (FIN) AF: 0.472 AC: 15106 AN: 31972

Middle Eastern (MID) AF: 0.288 AC: 729 AN: 2532

European-Non Finnish (NFE) AF: 0.404 AC: 148992 AN: 368754

Other (OTH) AF: 0.432 AC: 13109 AN: 30348

GnomAD4 genome AF: 0.411 AC: 62474 AN: 151946 Hom.: 13785 Cov.: 31 AF XY: 0.418 AC XY: 31017 AN XY: 74234

African (AFR) AF: 0.303 AC: 12540 AN: 41454

American (AMR) AF: 0.525 AC: 8016 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3466

East Asian (EAS) AF: 0.819 AC: 4221 AN: 5152

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4931 AN: 10542

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27822 AN: 67940

Other (OTH) AF: 0.400 AC: 845 AN: 2110

Alfa AF: 0.413 Hom.: 41378

Bravo AF: 0.416

Asia WGS AF: 0.595 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.86
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12904; hg19: chr1-155106697;