rs11168249

Variant names:

• chr12-47814585-T-C
• rs11168249
• NM_015401.5:c.19+5182A>G

Variant summary

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

The NM_015401.5(HDAC7):​c.19+5182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,144 control chromosomes in the GnomAD database, including 19,638 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 (19638 hom., cov: 33)
• Consequence: HDAC7 NM_015401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 62 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDAC7	NM_015401.5	c.19+5182A>G		intron_variant	Intron 1 of 25	ENST00000080059.12	NP_056216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC7	ENST00000080059.12	c.19+5182A>G		intron_variant	Intron 1 of 25	1	NM_015401.5	ENSP00000080059.7

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74865 AN: 152026 Hom.: 19619 Cov.: 33

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.492 AC: 74930 AN: 152144 Hom.: 19638 Cov.: 33 AF XY: 0.485 AC XY: 36054 AN XY: 74378

African (AFR) AF: 0.642 AC: 26637 AN: 41504

American (AMR) AF: 0.367 AC: 5619 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1747 AN: 3470

East Asian (EAS) AF: 0.0842 AC: 436 AN: 5180

South Asian (SAS) AF: 0.357 AC: 1721 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5464 AN: 10592

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31669 AN: 67968

Other (OTH) AF: 0.478 AC: 1009 AN: 2112

Alfa AF: 0.465 Hom.: 63369

Bravo AF: 0.485

Asia WGS AF: 0.256 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.32
PhyloP100		-0.088
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11168249; hg19: chr12-48208368; COSMIC: COSV50410184; COSMIC: COSV50410184;