rs2544038

chr12-47821450-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000434070.5(HDAC7):c.-99+11596A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,876 control chromosomes in the GnomAD database, including 13,289 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 0.41 (13289 hom., cov: 31)
• Consequence: HDAC7 ENST00000434070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDAC7	ENST00000434070.5	c.-99+11596A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62831 AN: 151758 Hom.: 13274 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.414 AC: 62883 AN: 151876 Hom.: 13289 Cov.: 31 AF XY: 0.409 AC XY: 30331 AN XY: 74238

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.398

Alfa AF: 0.422 Hom.: 2800

Bravo AF: 0.424

Asia WGS AF: 0.324 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	9.5
Dann	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2544038; hg19: chr12-48215233;