7-18954247-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The ENST00000432645.6(HDAC9):c.3030C>T(p.Phe1010=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,368,696 control chromosomes in the GnomAD database, including 395,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45700 hom., cov: 32)
  • Exomes 𝑓: 0.76 (350278 hom.)
• Consequence: HDAC9 ENST00000432645.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.337

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-18954247-C-T is Benign according to our data. Variant chr7-18954247-C-T is described in ClinVar as [Benign]. Clinvar id is 402925.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.337 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDAC9	NM_178425.4	c.3022+17C>T		intron_variant		ENST00000686413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC9	ENST00000686413.1	c.3022+17C>T		intron_variant			NM_178425.4	P4

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117682 AN: 151872 Hom.: 45654 Cov.: 32

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.762

GnomAD3 exomes AF: 0.776 AC: 122720 AN: 158116 Hom.: 47771 AF XY: 0.774 AC XY: 64314 AN XY: 83106

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.872

Gnomad ASJ exome AF: 0.772

Gnomad EAS exome AF: 0.713

Gnomad SAS exome AF: 0.779

Gnomad FIN exome AF: 0.761

Gnomad NFE exome AF: 0.752

Gnomad OTH exome AF: 0.758

GnomAD4 exome AF: 0.758 AC: 921878 AN: 1216708 Hom.: 350278 Cov.: 18 AF XY: 0.759 AC XY: 461809 AN XY: 608528

Gnomad4 AFR exome AF: 0.802

Gnomad4 AMR exome AF: 0.862

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.704

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.752

Gnomad4 OTH exome AF: 0.760

GnomAD4 genome AF: 0.775 AC: 117786 AN: 151988 Hom.: 45700 Cov.: 32 AF XY: 0.778 AC XY: 57762 AN XY: 74286

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.809

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.715

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.765

Alfa AF: 0.764 Hom.: 14897

Bravo AF: 0.778

Asia WGS AF: 0.761 AC: 2636 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 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	-0.86
Cadd	Benign	2.4
Dann	Benign	0.63

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: rs2389998; hg19: chr7-18993870; COSMIC: COSV67786182; COSMIC: COSV67786182;