chr12-47822647-A-T

Position:

• chr12-47822647-A-T

Variant summary

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

The ENST00000434070.5(HDAC7):​c.-99+10399T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,212 control chromosomes in the GnomAD database, including 11,454 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 0.38 (11454 hom., cov: 33)
• Consequence: HDAC7 ENST00000434070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.47822647A>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC7	ENST00000434070.5	c.-99+10399T>A		intron_variant		4		ENSP00000388561.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58114 AN: 152094 Hom.: 11445 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.382 AC: 58153 AN: 152212 Hom.: 11454 Cov.: 33 AF XY: 0.376 AC XY: 28006 AN XY: 74424

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.375

Alfa AF: 0.381 Hom.: 1381

Bravo AF: 0.394

Asia WGS AF: 0.308 AC: 1073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2544028; hg19: chr12-48216430;