rs9303692

Positions:

• chr17-35861492-G-A
• chr17-35861492-G-C
• chr17-35861492-G-T

Variant summary

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

The NM_152781.4(HEATR9):​c.756+1503C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,267,380 control chromosomes in the GnomAD database, including 15,047 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 0.16 (2184 hom., cov: 32)
  • Exomes 𝑓: 0.14 (12863 hom.)
• Consequence: HEATR9 NM_152781.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

HEATR9 (HGNC:26548): (HEAT repeat containing 9) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

TAF15 (HGNC:11547): (TATA-box binding protein associated factor 15) This gene encodes a member of the TET family of RNA-binding proteins. The encoded protein plays a role in RNA polymerase II gene transcription as a component of a distinct subset of multi-subunit transcription initiation factor TFIID complexes. Translocations involving this gene play a role in acute leukemia and extraskeletal myxoid chondrosarcoma, and mutations in this gene may play a role in amyotrophic lateral sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR9	NM_152781.4	c.756+1503C>T		intron_variant		ENST00000604834.6	NP_689994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEATR9	ENST00000604834.6	c.756+1503C>T		intron_variant		1	NM_152781.4	ENSP00000473941	P2
	ENST00000605454.1	n.75C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24306 AN: 152006 Hom.: 2172 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.143 AC: 159824 AN: 1115256 Hom.: 12863 Cov.: 15 AF XY: 0.142 AC XY: 80905 AN XY: 571008

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.343

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.160 AC: 24346 AN: 152124 Hom.: 2184 Cov.: 32 AF XY: 0.161 AC XY: 11954 AN XY: 74364

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.153

Alfa AF: 0.144 Hom.: 365

Bravo AF: 0.169

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.64
DANN	Benign	0.55

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: rs9303692; hg19: chr17-34188496;