rs1178127

Variant names:

• chr7-18727720-A-G
• rs1178127
• NM_178425.4:c.1872A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-18727720-A-G
• chr7-18727720-A-C
• chr7-18727720-A-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_178425.4(HDAC9):​c.1872A>G​(p.Pro624Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,564,104 control chromosomes in the GnomAD database, including 58,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5571 hom., cov: 33)
  • Exomes 𝑓: 0.27 (53218 hom.)
• Consequence: HDAC9 NM_178425.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28
• Publications: 25 publications found

Genes affected

HDAC9 (HGNC:14065): (histone deacetylase 9) 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 the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

HDAC9 Gene-Disease associations (from GenCC):

• auriculocondylar syndrome 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 7-18727720-A-G is Benign according to our data. Variant chr7-18727720-A-G is described in ClinVar as Benign. ClinVar VariationId is 402927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.28 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178425.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	NM_178425.4	MANE Select	c.1872A>G	p.Pro624Pro	synonymous	Exon 13 of 26	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.1863A>G	p.Pro621Pro	synonymous	Exon 13 of 26	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.1797A>G	p.Pro599Pro	synonymous	Exon 13 of 26	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.1872A>G	p.Pro624Pro	synonymous	Exon 13 of 26	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.1872A>G	p.Pro624Pro	synonymous	Exon 12 of 25	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.1863A>G	p.Pro621Pro	synonymous	Exon 13 of 26	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39631 AN: 151970 Hom.: 5564 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.260

GnomAD2 exomes AF: 0.293 AC: 59435 AN: 202658 AF XY: 0.295

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.268 AC: 377882 AN: 1412014 Hom.: 53218 Cov.: 33 AF XY: 0.270 AC XY: 189604 AN XY: 701116

African (AFR) AF: 0.220 AC: 6656 AN: 30264

American (AMR) AF: 0.280 AC: 9132 AN: 32630

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5511 AN: 24190

East Asian (EAS) AF: 0.527 AC: 19445 AN: 36918

South Asian (SAS) AF: 0.383 AC: 29840 AN: 77974

European-Finnish (FIN) AF: 0.306 AC: 16170 AN: 52778

Middle Eastern (MID) AF: 0.291 AC: 1627 AN: 5598

European-Non Finnish (NFE) AF: 0.250 AC: 273351 AN: 1093390

Other (OTH) AF: 0.277 AC: 16150 AN: 58272

GnomAD4 genome AF: 0.261 AC: 39668 AN: 152090 Hom.: 5571 Cov.: 33 AF XY: 0.267 AC XY: 19832 AN XY: 74344

African (AFR) AF: 0.218 AC: 9060 AN: 41518

American (AMR) AF: 0.268 AC: 4101 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3466

East Asian (EAS) AF: 0.535 AC: 2758 AN: 5154

South Asian (SAS) AF: 0.398 AC: 1919 AN: 4820

European-Finnish (FIN) AF: 0.305 AC: 3221 AN: 10560

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16777 AN: 67970

Other (OTH) AF: 0.259 AC: 548 AN: 2116

Alfa AF: 0.251 Hom.: 9393

Bravo AF: 0.258

Asia WGS AF: 0.415 AC: 1441 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.0
DANN	Benign	0.74
PhyloP100		2.3
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: rs1178127; hg19: chr7-18767343; COSMIC: COSV67772674;