chr1-155066988-C-T

Variant names:

• chr1-155066988-C-T
• rs114301457
• NM_005227.3:c.372C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_182689.2(EFNA4):​c.372C>T​(p.Phe124Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,612,832 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (41 hom.)
• Consequence: EFNA4 NM_182689.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.06
• Publications: 10 publications found

Genes affected

EFNA4 (HGNC:3224): (ephrin A4) 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 that has been implicated in proliferation and metastasis of several types of cancers. [provided by RefSeq, May 2022]

EFNA4-EFNA3 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-155066988-C-T is Benign according to our data. Variant chr1-155066988-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 710307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.
• BS2: High AC in GnomAd4 at 685 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182689.2. 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
	EFNA4	NM_005227.3	MANE Select	c.372C>T	p.Phe124Phe	synonymous	Exon 2 of 4	NP_005218.1
	EFNA4	NM_182689.2		c.372C>T	p.Phe124Phe	synonymous	Exon 2 of 4	NP_872631.1
	EFNA4	NM_182690.3		c.372C>T	p.Phe124Phe	synonymous	Exon 2 of 4	NP_872632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EFNA4	ENST00000368409.8	TSL:1 MANE Select	c.372C>T	p.Phe124Phe	synonymous	Exon 2 of 4	ENSP00000357394.3
	EFNA4	ENST00000359751.8	TSL:1	c.372C>T	p.Phe124Phe	synonymous	Exon 2 of 4	ENSP00000352789.4
	EFNA4-EFNA3	ENST00000505139.1	TSL:2	c.113+3052C>T		intron	N/A	ENSP00000426741.1

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 685 AN: 152202 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0169

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00528

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00464 AC: 1160 AN: 249734 AF XY: 0.00472

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.00216

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00552

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00512 AC: 7484 AN: 1460512 Hom.: 41 Cov.: 32 AF XY: 0.00512 AC XY: 3721 AN XY: 726482

African (AFR) AF: 0.000568 AC: 19 AN: 33438

American (AMR) AF: 0.00177 AC: 79 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26042

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.00363 AC: 312 AN: 86046

European-Finnish (FIN) AF: 0.0160 AC: 851 AN: 53256

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5762

European-Non Finnish (NFE) AF: 0.00536 AC: 5955 AN: 1111432

Other (OTH) AF: 0.00403 AC: 243 AN: 60306

GnomAD4 genome AF: 0.00450 AC: 685 AN: 152320 Hom.: 4 Cov.: 32 AF XY: 0.00483 AC XY: 360 AN XY: 74472

African (AFR) AF: 0.000842 AC: 35 AN: 41564

American (AMR) AF: 0.00477 AC: 73 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4828

European-Finnish (FIN) AF: 0.0169 AC: 179 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00528 AC: 359 AN: 68032

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00445 Hom.: 0

Bravo AF: 0.00314

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00463

EpiControl AF: 0.00445

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.2
DANN	Benign	0.82
PhyloP100		1.1
Mutation Taster		=99/1	polymorphism

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: rs114301457; hg19: chr1-155039464; COSMIC: COSV99664919; COSMIC: COSV99664919;