NM_139215.3:c.48-210C>A

Variant names:

• chr17-35819814-C-A
• rs4251737
• NM_139215.3:c.48-210C>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_139215.3(TAF15):​c.48-210C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,010 control chromosomes in the GnomAD database, including 2,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2134 hom., cov: 32)
• Consequence: TAF15 NM_139215.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.340
• Publications: 8 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

ENSG00000270894 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-35819814-C-A is Benign according to our data. Variant chr17-35819814-C-A is described in ClinVar as Benign. ClinVar VariationId is 1259825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139215.3. 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
	TAF15	NM_139215.3	MANE Select	c.48-210C>A		intron	N/A	NP_631961.1	Q92804-1
	TAF15	NM_003487.4		c.48-210C>A		intron	N/A	NP_003478.1	Q92804-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF15	ENST00000605844.6	TSL:1 MANE Select	c.48-210C>A		intron	N/A	ENSP00000474096.1	Q92804-1
	TAF15	ENST00000604841.5	TSL:1	c.48-210C>A		intron	N/A	ENSP00000474609.1	Q92804-2
	TAF15	ENST00000603393.6	TSL:1	n.48-210C>A		intron	N/A	ENSP00000474653.2	A0A075B7E4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24141 AN: 151892 Hom.: 2124 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.159 AC: 24178 AN: 152010 Hom.: 2134 Cov.: 32 AF XY: 0.160 AC XY: 11867 AN XY: 74274

African (AFR) AF: 0.195 AC: 8084 AN: 41456

American (AMR) AF: 0.171 AC: 2617 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3466

East Asian (EAS) AF: 0.328 AC: 1691 AN: 5158

South Asian (SAS) AF: 0.121 AC: 583 AN: 4818

European-Finnish (FIN) AF: 0.148 AC: 1560 AN: 10560

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8571 AN: 67966

Other (OTH) AF: 0.151 AC: 319 AN: 2108

Alfa AF: 0.139 Hom.: 2171

Bravo AF: 0.166

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

ClinVar submissions

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	-0.86
CADD	Benign	0.62
DANN	Benign	0.61
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4251737; hg19: chr17-34146818;