rs2544027

chr12-47822746-G-Achr12-47822746-G-T

Variant summary

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

The ENST00000434070.5(HDAC7):c.-99+10300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,122 control chromosomes in the GnomAD database, including 15,390 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 0.45 (15390 hom., cov: 33)
• Consequence: HDAC7 ENST00000434070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 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+10300C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67818 AN: 152004 Hom.: 15366 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.446 AC: 67890 AN: 152122 Hom.: 15390 Cov.: 33 AF XY: 0.441 AC XY: 32826 AN XY: 74364

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.455

Alfa AF: 0.235 Hom.: 456

Bravo AF: 0.454

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.4
Dann	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2544027; hg19: chr12-48216529;