rs3759407

Positions:

• chr12-47801286-G-A

Variant summary

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

The NM_015401.5(HDAC7):​c.70+938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,192 control chromosomes in the GnomAD database, including 949 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 0.075 (949 hom., cov: 33)
• Consequence: HDAC7 NM_015401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDAC7	NM_015401.5	c.70+938C>T		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+938C>T		intron_variant		1	NM_015401.5	ENSP00000080059.7
HDAC7	ENST00000380610.8	c.121+938C>T		intron_variant		2		ENSP00000369984.4

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11397 AN: 152074 Hom.: 939 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0415

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0750 AC: 11417 AN: 152192 Hom.: 949 Cov.: 33 AF XY: 0.0782 AC XY: 5821 AN XY: 74406

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.0513

Gnomad4 EAS AF: 0.0416

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.0782 Hom.: 1061

Bravo AF: 0.0897

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.57

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: rs3759407; hg19: chr12-48195069;