rs1176637542

Variant names:

• chr17-67825793-CCCGCCGCCA-C
• rs1176637542
• NM_182641.4:c.78_86delACCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr17-67825793-CCCGCCGCCA-C
• chr17-67825793-CCCGCCGCCA-CCCGCCGCCACCGCCGCCA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_182641.4(BPTF):​c.78_86delACCGCCGCC​(p.Pro27_Pro29del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000678 in 147,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P26P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BPTF NM_182641.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_182641.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182641.4. 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.78_86delACCGCCGCC	p.Pro27_Pro29del	disruptive_inframe_deletion	Exon 1 of 28	NP_872579.2
	BPTF	NM_001439139.1		c.78_86delACCGCCGCC	p.Pro27_Pro29del	disruptive_inframe_deletion	Exon 1 of 29	NP_001426068.1
	BPTF	NM_001439140.1		c.78_86delACCGCCGCC	p.Pro27_Pro29del	disruptive_inframe_deletion	Exon 1 of 31	NP_001426069.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPTF	ENST00000306378.11	TSL:1 MANE Select	c.78_86delACCGCCGCC	p.Pro27_Pro29del	disruptive_inframe_deletion	Exon 1 of 28	ENSP00000307208.6	Q12830-2
	BPTF	ENST00000582467.2	TSL:5	c.78_86delACCGCCGCC	p.Pro27_Pro29del	disruptive_inframe_deletion	Exon 1 of 32	ENSP00000463776.2	J3QQK4
	BPTF	ENST00000321892.8	TSL:5	c.78_86delACCGCCGCC	p.Pro27_Pro29del	disruptive_inframe_deletion	Exon 1 of 30	ENSP00000315454.4	Q12830-1

Frequencies

GnomAD3 genomes AF: 0.00000678 AC: 1 AN: 147558 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000244

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000225 AC: 2 AN: 887444 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 414640

African (AFR) AF: 0.00 AC: 0 AN: 16864

American (AMR) AF: 0.00 AC: 0 AN: 2786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6672

East Asian (EAS) AF: 0.00 AC: 0 AN: 6516

South Asian (SAS) AF: 0.00 AC: 0 AN: 17806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1896

European-Non Finnish (NFE) AF: 0.00000251 AC: 2 AN: 798194

Other (OTH) AF: 0.00 AC: 0 AN: 30600

GnomAD4 genome AF: 0.00000678 AC: 1 AN: 147558 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 71832

African (AFR) AF: 0.0000244 AC: 1 AN: 40976

American (AMR) AF: 0.00 AC: 0 AN: 14858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 5102

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66168

Other (OTH) AF: 0.00 AC: 0 AN: 2032

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21
Mutation Taster		=170/30	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1176637542; hg19: chr17-65821909;