Genetic Variant ENAH:c.1675+10delT (chr1-225498336-CA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_018212.6(ENAH):c.1675+10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,583,730 control chromosomes in the GnomAD database, including 131 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 81 hom. )

Consequence

ENAH
NM_018212.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.316

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 -10 ACMG points.

BP6

Variant 1-225498336-CA-C is Benign according to our data. Variant chr1-225498336-CA-C is described in ClinVar as [Benign]. Clinvar id is 780300.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2138/152164) while in subpopulation AFR AF = 0.046 (1908/41518). AF 95% confidence interval is 0.0442. There are 50 homozygotes in GnomAd4. There are 1074 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 2138 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6 link	c.1675+10delT		intron_variant	Intron 13 of 13	ENST00000366843.7	NP_060682.2	Q8N8S7-2A0A4D6J698

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7 link	c.1675+10delT		intron_variant	Intron 13 of 13	1	NM_018212.6	ENSP00000355808.2		Q8N8S7-2

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2124

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00640

AC:

1537

AN:

239996

AF XY:

0.00638

show subpopulations

Gnomad AFR exome

AF:

0.0448

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.000396

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000426

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00285

AC:

4079

AN:

1431566

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2365

AN XY:

713128

show subpopulations

Gnomad4 AFR exome

AF:

0.0467

AC:

1499

AN:

32124

Gnomad4 AMR exome

AF:

0.00399

AC:

167

AN:

41854

Gnomad4 ASJ exome

AF:

0.0000388

AC:

AN:

25754

Gnomad4 EAS exome

AF:

0.0000764

AC:

AN:

39274

Gnomad4 SAS exome

AF:

0.0219

AC:

1807

AN:

82680

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53276

Gnomad4 NFE exome

AF:

0.000281

AC:

307

AN:

1091528

Gnomad4 Remaining exome

AF:

0.00445

AC:

264

AN:

59388

Heterozygous variant carriers

160

319

479

638

798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0141

AC:

2138

AN:

152164

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1074

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0460

AC:

0.045956

AN:

0.045956

Gnomad4 AMR

AF:

0.00438

AC:

0.0043831

AN:

0.0043831

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000578

AC:

0.000578035

AN:

0.000578035

Gnomad4 SAS

AF:

0.0215

AC:

0.0214583

AN:

0.0214583

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000353

AC:

0.000352993

AN:

0.000352993

Gnomad4 OTH

AF:

0.0137

AC:

0.0137311

AN:

0.0137311

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

120

<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:

0.000742

Hom.:

Bravo

AF:

0.0148

Asia WGS

AF:

0.0110

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over