Genetic Variant ENAH:c.*4497T>G (chr1-225493278-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001420159.1(ENAH):c.*4497T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,180 control chromosomes in the GnomAD database, including 66,794 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 0.94 ( 66792 hom., cov: 31)

Exomes 𝑓: 1.0 ( 2 hom. )

Consequence

ENAH
NM_001420159.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

2 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001420159.1. 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.*4497T>G	3_prime_UTR	Exon 14 of 14	NP_060682.2
ENAH	NM_001420159.1		c.*4497T>G	3_prime_UTR	Exon 16 of 16	NP_001407088.1
ENAH	NM_001420160.1		c.*4497T>G	3_prime_UTR	Exon 15 of 15	NP_001407089.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ENAH	ENST00000366843.7	TSL:1 MANE Select	c.*4497T>G	3_prime_UTR	Exon 14 of 14	ENSP00000355808.2
ENAH	ENST00000366844.7	TSL:1	c.*4497T>G	3_prime_UTR	Exon 15 of 15	ENSP00000355809.2
ENAH	ENST00000696609.1		c.*4497T>G	3_prime_UTR	Exon 12 of 12	ENSP00000512753.1

Frequencies

GnomAD3 genomes

AF:

0.936

AC:

142389

AN:

152058

Hom.:

66742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.886

Gnomad AMI

AF:

0.982

Gnomad AMR

AF:

0.958

Gnomad ASJ

AF:

0.953

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.920

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.968

Gnomad NFE

AF:

0.959

Gnomad OTH

AF:

0.944

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

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)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.936

AC:

142496

AN:

152176

Hom.:

66792

Cov.:

AF XY:

0.937

AC XY:

69686

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.886

AC:

36777

AN:

41522

American (AMR)

AF:

0.958

AC:

14643

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.953

AC:

3309

AN:

3472

East Asian (EAS)

AF:

0.910

AC:

4701

AN:

5166

South Asian (SAS)

AF:

0.921

AC:

4429

AN:

4808

European-Finnish (FIN)

AF:

0.968

AC:

10262

AN:

10598

Middle Eastern (MID)

AF:

0.966

AC:

284

AN:

294

European-Non Finnish (NFE)

AF:

0.959

AC:

65201

AN:

68006

Other (OTH)

AF:

0.944

AC:

1994

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

454

908

1362

1816

2270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.952

Hom.:

107995

Bravo

AF:

0.934

Asia WGS

AF:

0.928

AC:

3228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.82

(source)

DANN

Benign

0.49

PhyloP100

-1.2

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

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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