rs2544037

Positions:

• chr12-47821397-A-G

Variant summary

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

The ENST00000434070.5(HDAC7):​c.-99+11649T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,676 control chromosomes in the GnomAD database, including 11,018 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 0.37 (11018 hom., cov: 31)
• Consequence: HDAC7 ENST00000434070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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 = 0.48 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+11649T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56414 AN: 151556 Hom.: 11010 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.372 AC: 56446 AN: 151676 Hom.: 11018 Cov.: 31 AF XY: 0.368 AC XY: 27270 AN XY: 74128

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.373

Alfa AF: 0.407 Hom.: 15203

Bravo AF: 0.382

Asia WGS AF: 0.305 AC: 1064 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	0.051
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2544037; hg19: chr12-48215180;