Genetic Variant ENAH:c.*5235T>C (chr1-225492540-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018212.6(ENAH):c.*5235T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 152,062 control chromosomes in the GnomAD database, including 772 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 0.086 ( 772 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENAH
NM_018212.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

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	Effect	Exon Rank	Protein
ENAH	NM_018212.6	MANE Select	c.*5235T>C	3_prime_UTR	Exon 14 of 14	NP_060682.2
ENAH	NM_001420159.1		c.*5235T>C	3_prime_UTR	Exon 16 of 16	NP_001407088.1
ENAH	NM_001420160.1		c.*5235T>C	3_prime_UTR	Exon 15 of 15	NP_001407089.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENAH	ENST00000366843.7	TSL:1 MANE Select	c.*5235T>C	3_prime_UTR	Exon 14 of 14	ENSP00000355808.2	Q8N8S7-2
ENAH	ENST00000366844.7	TSL:1	c.*5235T>C	3_prime_UTR	Exon 15 of 15	ENSP00000355809.2	Q8N8S7-1
ENAH	ENST00000696609.1		c.*5235T>C	3_prime_UTR	Exon 12 of 12	ENSP00000512753.1	A0A8Q3WLE0

Frequencies

GnomAD3 genomes

AF:

0.0860

AC:

13070

AN:

151944

Hom.:

773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0640

Gnomad EAS

AF:

0.0843

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.0808

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0798

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0860

AC:

13072

AN:

152062

Hom.:

772

Cov.:

AF XY:

0.0877

AC XY:

6522

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.0221

AC:

916

AN:

41448

American (AMR)

AF:

0.103

AC:

1569

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0640

AC:

222

AN:

3468

East Asian (EAS)

AF:

0.0843

AC:

436

AN:

5172

South Asian (SAS)

AF:

0.247

AC:

1186

AN:

4808

European-Finnish (FIN)

AF:

0.0808

AC:

854

AN:

10572

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7600

AN:

67980

Other (OTH)

AF:

0.0789

AC:

167

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

610

1220

1829

2439

3049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0989

Hom.:

170

Bravo

AF:

0.0817

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.45

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over