chr12-47821397-A-G

Variant names:

• chr12-47821397-A-G
• rs2544037
• ENST00000434070.5:c.-99+11649T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HDAC7	XM_047428980.1	c.-68T>C		upstream_gene_variant			XP_047284936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC7	ENST00000434070.5	c.-99+11649T>C		intron_variant	Intron 1 of 5	4		ENSP00000388561.1

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

African (AFR) AF: 0.267 AC: 11009 AN: 41304

American (AMR) AF: 0.489 AC: 7468 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2192 AN: 5152

South Asian (SAS) AF: 0.243 AC: 1164 AN: 4788

European-Finnish (FIN) AF: 0.373 AC: 3917 AN: 10502

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 27999 AN: 67898

Other (OTH) AF: 0.373 AC: 782 AN: 2098

Alfa AF: 0.405 Hom.: 17810

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
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs2544037; hg19: chr12-48215180;