Genetic Variant ENAH:c.*10018T>C (chr1-225487757-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.*10018T>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 0.661 in 152,050 control chromosomes in the GnomAD database, including 33,519 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 0.66 ( 33519 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

ENAH
NM_018212.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.524

Publications

9 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 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.*10018T>C	3_prime_UTR	Exon 14 of 14	NP_060682.2
ENAH	NM_001420159.1		c.*10018T>C	3_prime_UTR	Exon 16 of 16	NP_001407088.1
ENAH	NM_001420160.1		c.*10018T>C	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.*10018T>C	3_prime_UTR	Exon 14 of 14	ENSP00000355808.2
ENAH	ENST00000366844.7	TSL:1	c.*10018T>C	3_prime_UTR	Exon 15 of 15	ENSP00000355809.2
ENAH	ENST00000696609.1		c.*10018T>C	3_prime_UTR	Exon 12 of 12	ENSP00000512753.1

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

100439

AN:

151930

Hom.:

33526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.718

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.686

GnomAD4 exome

AF:

0.500

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.661

AC:

100470

AN:

152048

Hom.:

33519

Cov.:

AF XY:

0.656

AC XY:

48792

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.586

AC:

24289

AN:

41456

American (AMR)

AF:

0.666

AC:

10179

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.738

AC:

2560

AN:

3470

East Asian (EAS)

AF:

0.718

AC:

3717

AN:

5178

South Asian (SAS)

AF:

0.444

AC:

2141

AN:

4818

European-Finnish (FIN)

AF:

0.670

AC:

7075

AN:

10558

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.708

AC:

48154

AN:

67970

Other (OTH)

AF:

0.680

AC:

1433

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1796

3591

5387

7182

8978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.690

Hom.:

72495

Bravo

AF:

0.664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

(source)

DANN

Benign

0.74

PhyloP100

0.52

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