Genetic Variant NM_018212.6:c.794C>T (chr1-225519206-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018212.6(ENAH):c.794C>T(p.Ser265Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000248 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ENAH
NM_018212.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.92

Publications

3 publications found

Variant links:

Genes affected

ENAH (HGNC:18271): (ENAH actin regulator) This gene encodes a member of the enabled/ vasodilator-stimulated phosphoprotein. Members of this gene family are involved in actin-based motility. This protein is involved in regulating the assembly of actin filaments and modulates cell adhesion and motility. Alternate splice variants of this gene have been correlated with tumor invasiveness in certain tissues and these variants may serve as prognostic markers. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2016]

ENAH links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005862206).

BP6

Variant 1-225519206-G-A is Benign according to our data. Variant chr1-225519206-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 725097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 167 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018212.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ENAH	NM_018212.6	MANE Select	c.794C>T	p.Ser265Leu	missense	Exon 5 of 14	NP_060682.2
ENAH	NM_001420159.1		c.851C>T	p.Ser284Leu	missense	Exon 6 of 16	NP_001407088.1
ENAH	NM_001420160.1		c.794C>T	p.Ser265Leu	missense	Exon 5 of 15	NP_001407089.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENAH	ENST00000366843.7	TSL:1 MANE Select	c.794C>T	p.Ser265Leu	missense	Exon 5 of 14	ENSP00000355808.2	Q8N8S7-2
ENAH	ENST00000366844.7	TSL:1	c.794C>T	p.Ser265Leu	missense	Exon 5 of 15	ENSP00000355809.2	Q8N8S7-1
ENAH	ENST00000497899.6	TSL:1	c.644C>T	p.Ser215Leu	missense	Exon 4 of 4	ENSP00000489106.1	A0A0U1RQP7

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000343

AC:

AN:

251006

AF XY:

0.000251

show subpopulations

Gnomad AFR exome

AF:

0.00320

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000159

AC:

233

AN:

1461496

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.00344

AC:

115

AN:

33456

American (AMR)

AF:

0.000716

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000504

AC:

AN:

1111728

Other (OTH)

AF:

0.000397

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.00110

AC:

167

AN:

152330

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00301

AC:

125

AN:

41574

American (AMR)

AF:

0.00229

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000473

Hom.:

Bravo

AF:

0.00129

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.77

M_CAP

Benign

0.033

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.1

PhyloP100

5.9

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.097

Sift

Uncertain

0.017

Sift4G

Benign

0.28

Polyphen

0.10

Vest4

0.44

MVP

0.33

MPC

0.36

ClinPred

0.054

GERP RS

5.3

Varity_R

0.12

gMVP

0.44

Mutation Taster

=86/14

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