Genetic Variant NM_018212.6:c.*3302G>A (chr1-225494473-C-T) – 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.*3302G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,144 control chromosomes in the GnomAD database, including 53,513 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 0.84 ( 53513 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

ENAH
NM_018212.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

Publications

4 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=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.841 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.*3302G>A	3_prime_UTR	Exon 14 of 14	NP_060682.2
ENAH	NM_001420159.1		c.*3302G>A	3_prime_UTR	Exon 16 of 16	NP_001407088.1
ENAH	NM_001420160.1		c.*3302G>A	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.*3302G>A	3_prime_UTR	Exon 14 of 14	ENSP00000355808.2	Q8N8S7-2
ENAH	ENST00000366844.7	TSL:1	c.*3302G>A	3_prime_UTR	Exon 15 of 15	ENSP00000355809.2	Q8N8S7-1
ENAH	ENST00000696609.1		c.*3302G>A	3_prime_UTR	Exon 12 of 12	ENSP00000512753.1	A0A8Q3WLE0

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

127393

AN:

152026

Hom.:

53471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.821

Gnomad AMI

AF:

0.865

Gnomad AMR

AF:

0.850

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.826

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.918

Gnomad NFE

AF:

0.847

Gnomad OTH

AF:

0.859

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

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)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.838

AC:

127492

AN:

152144

Hom.:

53513

Cov.:

AF XY:

0.836

AC XY:

62225

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.821

AC:

34056

AN:

41500

American (AMR)

AF:

0.850

AC:

12993

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.887

AC:

3077

AN:

3468

East Asian (EAS)

AF:

0.825

AC:

4275

AN:

5180

South Asian (SAS)

AF:

0.674

AC:

3251

AN:

4820

European-Finnish (FIN)

AF:

0.888

AC:

9400

AN:

10586

Middle Eastern (MID)

AF:

0.912

AC:

268

AN:

294

European-Non Finnish (NFE)

AF:

0.847

AC:

57564

AN:

67990

Other (OTH)

AF:

0.860

AC:

1819

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1054

2108

3163

4217

5271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.844

Hom.:

17190

Bravo

AF:

0.839

Asia WGS

AF:

0.778

AC:

2703

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.75

(source)

DANN

Benign

0.74

PhyloP100

0.22

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