12-47829691-C-T

Variant names:

• chr12-47829691-C-T
• rs10747524
• ENST00000434070.5:c.-99+3355G>A

Variant summary

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

The ENST00000434070.5(HDAC7):​c.-99+3355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,932 control chromosomes in the GnomAD database, including 23,513 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 0.55 (23513 hom., cov: 31)
• Consequence: HDAC7 ENST00000434070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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]

LINC02354 (HGNC:53276): (long intergenic non-protein coding RNA 2354)

ACMG classification

Verdict is Benign. Variant got -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 = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC02354	XR_007063291.1	n.374+161C>T		intron_variant	Intron 1 of 1
LINC02354	XR_007063292.1	n.374+161C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDAC7	ENST00000434070.5	c.-99+3355G>A		intron_variant	Intron 1 of 5	4		ENSP00000388561.1
LINC02354	ENST00000546523.1	n.37+161C>T		intron_variant	Intron 1 of 1	3
LINC02354	ENST00000550684.1	n.60+2778C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83805 AN: 151814 Hom.: 23488 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.552 AC: 83867 AN: 151932 Hom.: 23513 Cov.: 31 AF XY: 0.547 AC XY: 40609 AN XY: 74254

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.525

Alfa AF: 0.536 Hom.: 36800

Bravo AF: 0.563

Asia WGS AF: 0.374 AC: 1302 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	6.2
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10747524; hg19: chr12-48223474;