rs1859281

chr12-47821966-G-A

Variant summary

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

The ENST00000434070.5(HDAC7):c.-99+11080C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,110 control chromosomes in the GnomAD database, including 1,036 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 0.10 (1036 hom., cov: 31)
• Consequence: HDAC7 ENST00000434070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 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+11080C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15437 AN: 151992 Hom.: 1035 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0897

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

GnomAD4 genome AF: 0.102 AC: 15450 AN: 152110 Hom.: 1036 Cov.: 31 AF XY: 0.102 AC XY: 7602 AN XY: 74362

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0830

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0883

Alfa AF: 0.0779 Hom.: 695

Bravo AF: 0.101

Asia WGS AF: 0.0460 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.8
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1859281; hg19: chr12-48215749;