rs12904

Positions:

• chr1-155134221-G-A
• chr1-155134221-G-C
• chr1-155134221-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFNA1	NM_004428.3	c.*154G>A		3_prime_UTR_variant	5/5	ENST00000368407.8	NP_004419.2
EFNA1	NM_182685.2	c.*154G>A		3_prime_UTR_variant	4/4		NP_872626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EFNA1	ENST00000368407.8	c.*154G>A		3_prime_UTR_variant	5/5	1	NM_004428.3	ENSP00000357392.3
EFNA1	ENST00000368406.2	c.*154G>A		3_prime_UTR_variant	4/4	1		ENSP00000357391.2
EFNA1	ENST00000469878.5	n.1023G>A		non_coding_transcript_exon_variant	4/4	3
EFNA1	ENST00000474413.5	n.997G>A		non_coding_transcript_exon_variant	5/5	3

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

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.866

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.432

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

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.400

Alfa AF: 0.415 Hom.: 26595

Bravo AF: 0.416

Asia WGS AF: 0.595 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs12904; hg19: chr1-155106697;