Genetic Variant HEATR9:c.756+1503C>T (chr17-35861492-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

9 publications found

Variant links:

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]

HEATR9 links:

ENSG00000271268 (HGNC:):

ENSG00000271268 links:

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]

TAF15 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

TAF15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HEATR9	NM_152781.4 link	c.756+1503C>T		intron_variant	Intron 8 of 14	ENST00000604834.6	NP_689994.2	A2RTY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR9	ENST00000604834.6 link	c.756+1503C>T		intron_variant	Intron 8 of 14	1	NM_152781.4	ENSP00000473941.1		A2RTY3-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24306

AN:

152006

Hom.:

2172

Cov.:

show subpopulations

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.:

AF XY:

0.142

AC XY:

80905

AN XY:

571008

show subpopulations

African (AFR)

AF:

0.195

AC:

5215

AN:

26804

American (AMR)

AF:

0.235

AC:

10382

AN:

44234

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

4023

AN:

24108

East Asian (EAS)

AF:

0.343

AC:

13050

AN:

38100

South Asian (SAS)

AF:

0.125

AC:

9960

AN:

79442

European-Finnish (FIN)

AF:

0.140

AC:

5972

AN:

42594

Middle Eastern (MID)

AF:

0.166

AC:

573

AN:

3452

European-Non Finnish (NFE)

AF:

0.128

AC:

103496

AN:

807480

Other (OTH)

AF:

0.146

AC:

7153

AN:

49042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7285

14569

21854

29138

36423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3418

6836

10254

13672

17090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.160

AC:

24346

AN:

152124

Hom.:

2184

Cov.:

AF XY:

0.161

AC XY:

11954

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.194

AC:

8069

AN:

41508

American (AMR)

AF:

0.180

AC:

2747

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

554

AN:

3468

East Asian (EAS)

AF:

0.331

AC:

1711

AN:

5172

South Asian (SAS)

AF:

0.127

AC:

613

AN:

4818

European-Finnish (FIN)

AF:

0.147

AC:

1555

AN:

10560

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.126

AC:

8572

AN:

68008

Other (OTH)

AF:

0.153

AC:

324

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1035

2069

3104

4138

5173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.145

Hom.:

386

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

(source)

DANN

Benign

0.55

PhyloP100

1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over