12-47802156-G-C

Position:

• chr12-47802156-G-C

Variant summary

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

The NM_015401.5(HDAC7):​c.70+68C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,502,050 control chromosomes in the GnomAD database, including 172,388 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 0.49 (18917 hom., cov: 31)
  • Exomes 𝑓: 0.47 (153471 hom.)
• Consequence: HDAC7 NM_015401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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]

LOC124902926 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC7	NM_015401.5	c.70+68C>G		intron_variant		ENST00000080059.12	NP_056216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDAC7	ENST00000080059.12	c.70+68C>G		intron_variant		1	NM_015401.5	ENSP00000080059.7
HDAC7	ENST00000380610.8	c.121+68C>G		intron_variant		2		ENSP00000369984.4

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73989 AN: 151840 Hom.: 18905 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.469 AC: 632873 AN: 1350092 Hom.: 153471 AF XY: 0.467 AC XY: 312579 AN XY: 669450

Gnomad4 AFR exome AF: 0.582

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.0853

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.540

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.487 AC: 74046 AN: 151958 Hom.: 18917 Cov.: 31 AF XY: 0.481 AC XY: 35695 AN XY: 74258

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.480

Alfa AF: 0.334 Hom.: 851

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2525051; hg19: chr12-48195939;