rs2544038

Variant names:

• chr12-47821450-T-C
• rs2544038
• ENST00000434070.5:c.-99+11596A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000434070.5(HDAC7):​c.-99+11596A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,876 control chromosomes in the GnomAD database, including 13,289 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 0.41 (13289 hom., cov: 31)
• Consequence: HDAC7 ENST00000434070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 13 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 = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC7	XM_047428980.1	c.-121A>G		upstream_gene_variant			XP_047284936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC7	ENST00000434070.5	c.-99+11596A>G		intron_variant	Intron 1 of 5	4		ENSP00000388561.1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62831 AN: 151758 Hom.: 13274 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.414 AC: 62883 AN: 151876 Hom.: 13289 Cov.: 31 AF XY: 0.409 AC XY: 30331 AN XY: 74238

African (AFR) AF: 0.361 AC: 14922 AN: 41386

American (AMR) AF: 0.509 AC: 7774 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1520 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2047 AN: 5158

South Asian (SAS) AF: 0.273 AC: 1312 AN: 4810

European-Finnish (FIN) AF: 0.413 AC: 4352 AN: 10538

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29543 AN: 67932

Other (OTH) AF: 0.398 AC: 840 AN: 2108

Alfa AF: 0.424 Hom.: 21014

Bravo AF: 0.424

Asia WGS AF: 0.324 AC: 1128 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	9.5
DANN	Benign	0.79
PhyloP100		0.021

Splicing

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

Other links and lift over

dbSNP: rs2544038; hg19: chr12-48215233;