rs753044214

Positions:

• chr17-67903834-CA-C
• chr17-67903834-CA-CAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BS1 BS2

The NM_182641.4(BPTF):​c.2598del​(p.Glu867ArgfsTer16) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000345 in 1,537,806 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: BPTF NM_182641.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22

Genes affected

BPTF (HGNC:3581): (bromodomain PHD finger transcription factor) This gene was identified by the reactivity of its encoded protein to a monoclonal antibody prepared against brain homogenates from patients with Alzheimer's disease. Analysis of the original protein (fetal Alz-50 reactive clone 1, or FAC1), identified as an 810 aa protein containing a DNA-binding domain and a zinc finger motif, suggested it might play a role in the regulation of transcription. High levels of FAC1 were detected in fetal brain and in patients with neurodegenerative diseases. The protein encoded by this gene is actually much larger than originally thought, and it also contains a C-terminal bromodomain characteristic of proteins that regulate transcription during proliferation. The encoded protein is highly similar to the largest subunit of the Drosophila NURF (nucleosome remodeling factor) complex. In Drosophila, the NURF complex, which catalyzes nucleosome sliding on DNA and interacts with sequence-specific transcription factors, is necessary for the chromatin remodeling required for transcription. Two alternative transcripts encoding different isoforms have been described completely. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00038 (528/1390608) while in subpopulation AMR AF= 0.00242 (88/36388). AF 95% confidence interval is 0.00201. There are 0 homozygotes in gnomad4_exome. There are 275 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 528 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPTF	NM_182641.4	c.2598del	p.Glu867ArgfsTer16	frameshift_variant	8/28	ENST00000306378.11	NP_872579.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPTF	ENST00000306378.11	c.2598del	p.Glu867ArgfsTer16	frameshift_variant	8/28	1	NM_182641.4	ENSP00000307208

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000211

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000380 AC: 528 AN: 1390608 Hom.: 0 Cov.: 29 AF XY: 0.000398 AC XY: 275 AN XY: 691378

Gnomad4 AFR exome AF: 0.000594

Gnomad4 AMR exome AF: 0.00242

Gnomad4 ASJ exome AF: 0.000567

Gnomad4 EAS exome AF: 0.000429

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.000252

Gnomad4 NFE exome AF: 0.000226

Gnomad4 OTH exome AF: 0.000524

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147198 Hom.: 0 Cov.: 32 AF XY: 0.0000140 AC XY: 1 AN XY: 71504

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000211

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00149 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs753044214; hg19: chr17-65899950;