Variant 7-18591652-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_178425.4(HDAC9):c.542+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00976 in 1,612,090 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 32)

Exomes 𝑓: 0.010 ( 87 hom. )

Consequence

HDAC9
NM_178425.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.50

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-18591652-G-A is Benign according to our data. Variant chr7-18591652-G-A is described in ClinVar as [Benign]. Clinvar id is 770372.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1065 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC9	NM_178425.4 linkuse as main transcript	c.542+10G>A		intron_variant		ENST00000686413.1	NP_848512.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC9	ENST00000686413.1 linkuse as main transcript	c.542+10G>A		intron_variant			NM_178425.4	ENSP00000509161	P4	Q9UKV0-7

Frequencies

GnomAD3 genomes

AF:

0.00700

AC:

1065

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00668

AC:

1655

AN:

247656

Hom.:

AF XY:

0.00654

AC XY:

878

AN XY:

134302

show subpopulations

Gnomad AFR exome

AF:

0.00278

Gnomad AMR exome

AF:

0.00447

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00454

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.00634

GnomAD4 exome

AF:

0.0100

AC:

14662

AN:

1459838

Hom.:

Cov.:

AF XY:

0.00958

AC XY:

6955

AN XY:

726146

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.00476

Gnomad4 ASJ exome

AF:

0.000231

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000698

Gnomad4 FIN exome

AF:

0.00473

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00836

GnomAD4 genome

AF:

0.00699

AC:

1065

AN:

152252

Hom.:

Cov.:

AF XY:

0.00613

AC XY:

456

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00594

Hom.:

Bravo

AF:

0.00707

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.73

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