Genetic Variant NM_018212.6: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

Publications

1 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 -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 VariationId 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 passed quality control check.

BS2

High AC in GnomAd4 at 2138 AD gene.

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.1675+10delT	intron	N/A	NP_060682.2
ENAH	NM_001420159.1		c.2479+10delT	intron	N/A	NP_001407088.1
ENAH	NM_001420160.1		c.2422+10delT	intron	N/A	NP_001407089.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ENAH	ENST00000366843.7	TSL:1 MANE Select	c.1675+10delT	intron	N/A	ENSP00000355808.2	Q8N8S7-2
ENAH	ENST00000366844.7	TSL:1	c.1738+10delT	intron	N/A	ENSP00000355809.2	Q8N8S7-1
ENAH	ENST00000893225.1		c.2422+10delT	intron	N/A	ENSP00000563284.1

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

African (AFR)

AF:

0.0467

AC:

1499

AN:

32124

American (AMR)

AF:

0.00399

AC:

167

AN:

41854

Ashkenazi Jewish (ASJ)

AF:

0.0000388

AC:

AN:

25754

East Asian (EAS)

AF:

0.0000764

AC:

AN:

39274

South Asian (SAS)

AF:

0.0219

AC:

1807

AN:

82680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53276

Middle Eastern (MID)

AF:

0.00545

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.000281

AC:

307

AN:

1091528

Other (OTH)

AF:

0.00445

AC:

264

AN:

59388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

160

319

479

638

798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.0460

AC:

1908

AN:

41518

American (AMR)

AF:

0.00438

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.0215

AC:

103

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

67990

Other (OTH)

AF:

0.0137

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.32

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over