rs4251719

Variant names:

• chr17-35815358-G-A
• rs4251719
• NM_139215.3:c.8-2358G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139215.3(TAF15):​c.8-2358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,186 control chromosomes in the GnomAD database, including 2,186 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 (2186 hom., cov: 32)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 13 publications found

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]

TAF15 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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
TAF15	NM_139215.3	c.8-2358G>A		intron_variant	Intron 1 of 15	ENST00000605844.6	NP_631961.1
TAF15	NM_003487.4	c.8-2358G>A		intron_variant	Intron 1 of 15		NP_003478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF15	ENST00000605844.6	c.8-2358G>A		intron_variant	Intron 1 of 15	1	NM_139215.3	ENSP00000474096.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24411 AN: 152068 Hom.: 2174 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.161 AC: 24455 AN: 152186 Hom.: 2186 Cov.: 32 AF XY: 0.162 AC XY: 12024 AN XY: 74414

African (AFR) AF: 0.196 AC: 8127 AN: 41524

American (AMR) AF: 0.181 AC: 2765 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1713 AN: 5178

South Asian (SAS) AF: 0.125 AC: 601 AN: 4824

European-Finnish (FIN) AF: 0.147 AC: 1556 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8614 AN: 68018

Other (OTH) AF: 0.153 AC: 323 AN: 2112

Alfa AF: 0.138 Hom.: 886

Bravo AF: 0.169

Asia WGS AF: 0.194 AC: 674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-0.12

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: rs4251719; hg19: chr17-34142362;