rs753502762

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005864.4(EFS):c.1028G>A(p.Arg343His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000659 in 515,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R343C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

EFS
NM_005864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0130

Publications

0 publications found

Variant links:

Genes affected

EFS (HGNC:16898): (embryonal Fyn-associated substrate) The protein encoded by this gene is a member of the CAS (CRK-associated substrate) family of adaptor proteins which typically serve as scaffolds for the assembly of larger signaling complexes. These complexes form at the cell surface where integrin binding leads to the subsequent phosphorylation of a CAS protein. Additional binding of SRC family kinases leads to CAS hyperphosphorylation and the creation of binding sites for CRK and other proteins that cause actin cytoskeleton reorganization. This gene plays a role in integrin-mediated cell attachment, spreading, and migration and also plays a role in both normal and malignant cellular transformation. This broadly expressed gene has been shown to play a role in neurite outgrowth and its expression in the thymus and lymphocytes is important for T cell maturation and the development of immunological self-tolerance. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2020]

EFS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047722876).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFS	NM_005864.4	MANE Select	c.1028G>A	p.Arg343His	missense	Exon 4 of 6	NP_005855.1	O43281-1
EFS	NM_032459.3		c.749G>A	p.Arg250His	missense	Exon 3 of 5	NP_115835.1	O43281-2
EFS	NM_001385607.1		c.749G>A	p.Arg250His	missense	Exon 3 of 4	NP_001372536.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EFS	ENST00000216733.8	TSL:1 MANE Select	c.1028G>A	p.Arg343His	missense	Exon 4 of 6	ENSP00000216733.3	O43281-1
EFS	ENST00000351354.3	TSL:1	c.749G>A	p.Arg250His	missense	Exon 3 of 5	ENSP00000340607.3	O43281-2
EFS	ENST00000923553.1		c.1028G>A	p.Arg343His	missense	Exon 4 of 5	ENSP00000593612.1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000338

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000196

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000481

AC:

AN:

187276

AF XY:

0.0000478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000504

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000826

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000675

Gnomad OTH exome

AF:

0.000243

GnomAD4 exome

AF:

0.0000792

AC:

AN:

404264

Hom.:

Cov.:

AF XY:

0.0000919

AC XY:

AN XY:

217592

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

10322

American (AMR)

AF:

0.0000972

AC:

AN:

20584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8376

East Asian (EAS)

AF:

0.000120

AC:

AN:

8324

South Asian (SAS)

AF:

0.000174

AC:

AN:

45952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24890

Middle Eastern (MID)

AF:

0.000795

AC:

AN:

2516

European-Non Finnish (NFE)

AF:

0.0000485

AC:

AN:

267846

Other (OTH)

AF:

0.000259

AC:

AN:

15454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111628

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

54990

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30930

American (AMR)

AF:

0.00

AC:

AN:

11948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2790

East Asian (EAS)

AF:

0.00

AC:

AN:

3328

South Asian (SAS)

AF:

0.000338

AC:

AN:

2960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

202

European-Non Finnish (NFE)

AF:

0.0000196

AC:

AN:

50922

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000334

Hom.:

ExAC

AF:

0.0000503

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.048

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.78

M_CAP

Benign

0.018

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

-0.013

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.56

REVEL

Benign

0.027

Sift

Benign

0.54

Sift4G

Benign

0.19

Polyphen

0.022

Vest4

0.097

MutPred

0.28

Loss of methylation at R343 (P = 0.0388)

MVP

0.62

MPC

0.14

ClinPred

0.041

GERP RS

3.8

Varity_R

0.037

gMVP

0.35

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over