17-35817456-A-G

Position:

• chr17-35817456-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139215.3(TAF15):​c.8-260A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 467,098 control chromosomes in the GnomAD database, including 1,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (274 hom., cov: 31)
  • Exomes 𝑓: 0.054 (733 hom.)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0900

Genes affected

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]

ENSG00000270871 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-35817456-A-G is Benign according to our data. Variant chr17-35817456-A-G is described in ClinVar as [Benign]. Clinvar id is 1282925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF15	NM_139215.3	c.8-260A>G		intron_variant		ENST00000605844.6	NP_631961.1
TAF15	NM_003487.4	c.8-260A>G		intron_variant			NP_003478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF15	ENST00000605844.6	c.8-260A>G		intron_variant		1	NM_139215.3	ENSP00000474096.1

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8137 AN: 152052 Hom.: 273 Cov.: 31

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0432

GnomAD4 exome AF: 0.0537 AC: 16903 AN: 314928 Hom.: 733 AF XY: 0.0585 AC XY: 9782 AN XY: 167106

Gnomad4 AFR exome AF: 0.0629

Gnomad4 AMR exome AF: 0.0235

Gnomad4 ASJ exome AF: 0.0229

Gnomad4 EAS exome AF: 0.00755

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0351

Gnomad4 NFE exome AF: 0.0487

Gnomad4 OTH exome AF: 0.0434

GnomAD4 genome AF: 0.0534 AC: 8133 AN: 152170 Hom.: 274 Cov.: 31 AF XY: 0.0540 AC XY: 4021 AN XY: 74400

Gnomad4 AFR AF: 0.0649

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.0305

Gnomad4 NFE AF: 0.0519

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0556 Hom.: 47

Bravo AF: 0.0492

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
DANN	Benign	0.80

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: rs7209512; hg19: chr17-34144460;