7-18591652-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.50

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]

ACMG classification

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 GnomAd at 1065 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC9	ENST00000686413.1	c.542+10G>A		intron_variant			NM_178425.4	P4

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 1065 AN: 152134 Hom.: 6 Cov.: 32

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.: 6 AF XY: 0.00654 AC XY: 878 AN XY: 134302

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.: 87 Cov.: 34 AF XY: 0.00958 AC XY: 6955 AN XY: 726146

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.: 6 Cov.: 32 AF XY: 0.00613 AC XY: 456 AN XY: 74432

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.: 1

Bravo AF: 0.00707

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	17
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

Other links and lift over

dbSNP: rs150067220; hg19: chr7-18631275;