rs7216064

Variant names:

• chr17-67902693-G-A
• rs7216064
• NM_182641.4:c.2544-1096G>A

Variant summary

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

The NM_001439139.1(BPTF):​c.2733-1096G>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_001439139.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• Publications: 54 publications found

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]

BPTF Gene-Disease associations (from GenCC):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Illumina
• neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439139.1. 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
	BPTF	NM_182641.4	MANE Select	c.2544-1096G>A		intron	N/A	NP_872579.2
	BPTF	NM_001439139.1		c.2733-1096G>A		intron	N/A	NP_001426068.1
	BPTF	NM_001439140.1		c.2922-1096G>A		intron	N/A	NP_001426069.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPTF	ENST00000306378.11	TSL:1 MANE Select	c.2544-1096G>A		intron	N/A	ENSP00000307208.6
	BPTF	ENST00000342579.8	TSL:1	c.2613-1096G>A		intron	N/A	ENSP00000343837.5
	BPTF	ENST00000424123.7	TSL:1	c.2505-1096G>A		intron	N/A	ENSP00000388405.3

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

African (AFR) AF: 0.185 AC: 7666 AN: 41448

American (AMR) AF: 0.263 AC: 4022 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 595 AN: 3468

East Asian (EAS) AF: 0.674 AC: 3461 AN: 5134

South Asian (SAS) AF: 0.250 AC: 1201 AN: 4812

European-Finnish (FIN) AF: 0.245 AC: 2587 AN: 10568

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13788 AN: 67968

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.209 Hom.: 13874

Bravo AF: 0.223

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

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: rs7216064; hg19: chr17-65898809;