rs7216064

Positions:

• chr17-67902693-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182641.4(BPTF):​c.2544-1096G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,994 control chromosomes in the GnomAD database, including 4,410 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 0.22 (4410 hom., cov: 32)
• Consequence: BPTF NM_182641.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPTF	NM_182641.4	c.2544-1096G>A		intron_variant		ENST00000306378.11	NP_872579.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPTF	ENST00000306378.11	c.2544-1096G>A		intron_variant		1	NM_182641.4	ENSP00000307208

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33906 AN: 151874 Hom.: 4405 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.223 AC: 33922 AN: 151994 Hom.: 4410 Cov.: 32 AF XY: 0.229 AC XY: 17024 AN XY: 74294

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.226

Alfa AF: 0.205 Hom.: 5145

Bravo AF: 0.223

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.43

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: rs7216064; hg19: chr17-65898809;