rs150067220

Variant names:

• chr7-18591652-G-A
• rs150067220
• NM_178425.4:c.542+10G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-18591652-G-A
• chr7-18591652-G-C
• chr7-18591652-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_178425.4(HDAC9):​c.542+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00976 in 1,612,090 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (6 hom., cov: 32)
  • Exomes 𝑓: 0.010 (87 hom.)
• Consequence: HDAC9 NM_178425.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.50
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-18591652-G-A is Benign according to our data. Variant chr7-18591652-G-A is described in ClinVar as Benign. ClinVar VariationId is 770372.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1065 AD gene.

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.542+10G>A		intron	N/A	NP_848512.1	Q9UKV0-7
	HDAC9	NM_178423.3		c.533+10G>A		intron	N/A	NP_848510.1	Q9UKV0-5
	HDAC9	NM_001321868.2		c.599+10G>A		intron	N/A	NP_001308797.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDAC9	ENST00000686413.1	MANE Select	c.542+10G>A		intron	N/A	ENSP00000509161.1	Q9UKV0-7
	HDAC9	ENST00000441542.7	TSL:1	c.542+10G>A		intron	N/A	ENSP00000408617.2	Q9UKV0-7
	HDAC9	ENST00000406451.8	TSL:1	c.533+10G>A		intron	N/A	ENSP00000384657.3	Q9UKV0-5

Frequencies

GnomAD3 genomes AF: 0.00700 AC: 1065 AN: 152134 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00668 AC: 1655 AN: 247656 AF XY: 0.00654

Gnomad AFR exome AF: 0.00278

Gnomad AMR exome AF: 0.00447

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00454

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00634

GnomAD4 exome AF: 0.0100 AC: 14662 AN: 1459838 Hom.: 87 Cov.: 34 AF XY: 0.00958 AC XY: 6955 AN XY: 726146

African (AFR) AF: 0.00251 AC: 84 AN: 33418

American (AMR) AF: 0.00476 AC: 212 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.000231 AC: 6 AN: 26016

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.0000698 AC: 6 AN: 85990

European-Finnish (FIN) AF: 0.00473 AC: 252 AN: 53304

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.0122 AC: 13594 AN: 1110810

Other (OTH) AF: 0.00836 AC: 504 AN: 60304

GnomAD4 genome AF: 0.00699 AC: 1065 AN: 152252 Hom.: 6 Cov.: 32 AF XY: 0.00613 AC XY: 456 AN XY: 74432

African (AFR) AF: 0.00260 AC: 108 AN: 41558

American (AMR) AF: 0.00628 AC: 96 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0119 AC: 812 AN: 68004

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00742 Hom.: 3

Bravo AF: 0.00707

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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: rs150067220; hg19: chr7-18631275;