Genetic Variant HDAC7:c.70+68C>G (chr12-47802156-G-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_015401.5(HDAC7):c.70+68C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,502,050 control chromosomes in the GnomAD database, including 172,388 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 0.49 ( 18917 hom., cov: 31)

Exomes 𝑓: 0.47 ( 153471 hom. )

Consequence

HDAC7
NM_015401.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.341

Publications

14 publications found

Variant links:

Genes affected

HDAC7 (HGNC:14067): (histone deacetylase 7) Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene has sequence homology to members of the histone deacetylase family. This gene is orthologous to mouse HDAC7 gene whose protein promotes repression mediated via the transcriptional corepressor SMRT. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HDAC7 links:

LOC124902926 (HGNC:):

LOC124902926 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HDAC7	NM_015401.5	MANE Select	c.70+68C>G	intron	N/A	NP_056216.2	Q8WUI4-5
HDAC7	NM_001368046.1		c.70+68C>G	intron	N/A	NP_001354975.1
HDAC7	NM_001308090.2		c.20-3184C>G	intron	N/A	NP_001295019.1	Q8WUI4-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HDAC7	ENST00000080059.12	TSL:1 MANE Select	c.70+68C>G	intron	N/A	ENSP00000080059.7	Q8WUI4-5
HDAC7	ENST00000380610.8	TSL:2	c.121+68C>G	intron	N/A	ENSP00000369984.4	J3KPH8
HDAC7	ENST00000354334.7	TSL:1	c.70+68C>G	intron	N/A	ENSP00000351326.3	Q8WUI4-7

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73989

AN:

151840

Hom.:

18905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.576

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.0848

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.479

GnomAD4 exome

AF:

0.469

AC:

632873

AN:

1350092

Hom.:

153471

AF XY:

0.467

AC XY:

312579

AN XY:

669450

show subpopulations

African (AFR)

AF:

0.582

AC:

18026

AN:

30956

American (AMR)

AF:

0.267

AC:

9982

AN:

37438

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

12053

AN:

24718

East Asian (EAS)

AF:

0.0853

AC:

3138

AN:

36806

South Asian (SAS)

AF:

0.393

AC:

31076

AN:

79046

European-Finnish (FIN)

AF:

0.540

AC:

25861

AN:

47894

Middle Eastern (MID)

AF:

0.516

AC:

2879

AN:

5582

European-Non Finnish (NFE)

AF:

0.489

AC:

504121

AN:

1031292

Other (OTH)

AF:

0.457

AC:

25737

AN:

56360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

16044

32088

48133

64177

80221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14530

29060

43590

58120

72650

<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:

0.487

AC:

74046

AN:

151958

Hom.:

18917

Cov.:

AF XY:

0.481

AC XY:

35695

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.576

AC:

23863

AN:

41418

American (AMR)

AF:

0.369

AC:

5639

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

1744

AN:

3470

East Asian (EAS)

AF:

0.0852

AC:

438

AN:

5142

South Asian (SAS)

AF:

0.366

AC:

1768

AN:

4828

European-Finnish (FIN)

AF:

0.537

AC:

5668

AN:

10550

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.490

AC:

33294

AN:

67952

Other (OTH)

AF:

0.480

AC:

1013

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1911

3822

5732

7643

9554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.334

Hom.:

851

Bravo

AF:

0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.1

(source)

DANN

Benign

0.38

PhyloP100

0.34

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over