Variant 7-18727720-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_178425.4(HDAC9):c.1872A>G(p.Pro624Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,564,104 control chromosomes in the GnomAD database, including 58,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5571 hom., cov: 33)

Exomes 𝑓: 0.27 ( 53218 hom. )

Consequence

HDAC9
NM_178425.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

HDAC9 (HGNC:14065): (histone deacetylase 9) 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 the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

HDAC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 7-18727720-A-G is Benign according to our data. Variant chr7-18727720-A-G is described in ClinVar as [Benign]. Clinvar id is 402927.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4 link	c.1872A>G	p.Pro624Pro	synonymous_variant	13/26	ENST00000686413.1	NP_848512.1	Q9UKV0-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1 link	c.1872A>G	p.Pro624Pro	synonymous_variant	13/26		NM_178425.4	ENSP00000509161.1		Q9UKV0-7

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39631

AN:

151970

Hom.:

5564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.260

GnomAD3 exomes

AF:

0.293

AC:

59435

AN:

202658

Hom.:

9452

AF XY:

0.295

AC XY:

32778

AN XY:

111218

show subpopulations

Gnomad AFR exome

AF:

0.218

Gnomad AMR exome

AF:

0.285

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.549

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.249

Gnomad OTH exome

AF:

0.274

GnomAD4 exome

AF:

0.268

AC:

377882

AN:

1412014

Hom.:

53218

Cov.:

AF XY:

0.270

AC XY:

189604

AN XY:

701116

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.527

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.261

AC:

39668

AN:

152090

Hom.:

5571

Cov.:

AF XY:

0.267

AC XY:

19832

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.535

Gnomad4 SAS

AF:

0.398

Gnomad4 FIN

AF:

0.305

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.249

Hom.:

6211

Bravo

AF:

0.258

Asia WGS

AF:

0.415

AC:

1441

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.0

DANN

Benign

0.74

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