dbSNP rs954534: ENAH:c.*9147A>G (chr1-225488628-T-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_018212.6(ENAH):c.*9147A>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 0.0937 in 152,242 control chromosomes in the GnomAD database, including 826 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 0.094 ( 826 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: 0.381

Publications

6 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:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6 link	c.*9147A>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000366843.7	NP_060682.2	Q8N8S7-2A0A4D6J698

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENAH	ENST00000366843.7 link	c.*9147A>G	3_prime_UTR_variant	Exon 14 of 14	1	NM_018212.6	ENSP00000355808.2	Q8N8S7-2
ENAH	ENST00000366844.7 link	c.*9147A>G	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000355809.2	Q8N8S7-1
ENAH	ENST00000696609.1 link	c.*9147A>G	3_prime_UTR_variant	Exon 12 of 12			ENSP00000512753.1	A0A8Q3WLE0

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14265

AN:

152122

Hom.:

827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0660

Gnomad EAS

AF:

0.0845

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.0806

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.0829

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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)

AF:

0.500

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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:

0.0937

AC:

14271

AN:

152240

Hom.:

826

Cov.:

AF XY:

0.0957

AC XY:

7127

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0485

AC:

2016

AN:

41568

American (AMR)

AF:

0.107

AC:

1632

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0660

AC:

229

AN:

3470

East Asian (EAS)

AF:

0.0845

AC:

438

AN:

5184

South Asian (SAS)

AF:

0.247

AC:

1193

AN:

4822

European-Finnish (FIN)

AF:

0.0806

AC:

854

AN:

10590

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.112

AC:

7612

AN:

67992

Other (OTH)

AF:

0.0820

AC:

173

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

659

1318

1978

2637

3296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.104

Hom.:

1125

Bravo

AF:

0.0901

Asia WGS

AF:

0.146

AC:

507

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.8

(source)

DANN

Benign

0.73

PhyloP100

0.38

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over