Genetic Variant NM_018212.6:c.*8906C>T (chr1-225488869-G-A) – 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.*8906C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,204 control chromosomes in the GnomAD database, including 1,853 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 0.13 ( 1853 hom., cov: 32)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

ENAH
NM_018212.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0570

Publications

8 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6 link	c.*8906C>T		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.*8906C>T	3_prime_UTR_variant	Exon 14 of 14	1	NM_018212.6	ENSP00000355808.2	Q8N8S7-2
ENAH	ENST00000366844.7 link	c.*8906C>T	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000355809.2	Q8N8S7-1
ENAH	ENST00000696609.1 link	c.*8906C>T	3_prime_UTR_variant	Exon 12 of 12			ENSP00000512753.1	A0A8Q3WLE0

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20140

AN:

152080

Hom.:

1856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.384

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

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)

AF:

0.167

AC:

AN:

Other (OTH)

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: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.132

AC:

20129

AN:

152198

Hom.:

1853

Cov.:

AF XY:

0.136

AC XY:

10144

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0314

AC:

1304

AN:

41538

American (AMR)

AF:

0.142

AC:

2173

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0651

AC:

226

AN:

3470

East Asian (EAS)

AF:

0.383

AC:

1978

AN:

5168

South Asian (SAS)

AF:

0.133

AC:

642

AN:

4820

European-Finnish (FIN)

AF:

0.214

AC:

2260

AN:

10576

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.162

AC:

11045

AN:

68008

Other (OTH)

AF:

0.131

AC:

278

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

861

1722

2583

3444

4305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.140

Hom.:

1073

Bravo

AF:

0.126

Asia WGS

AF:

0.222

AC:

775

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.62

(source)

DANN

Benign

0.52

PhyloP100

0.057

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over