17-67825856-C-G

Variant names:

• chr17-67825856-C-G
• rs2055942962
• NM_182641.4:c.132C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_182641.4(BPTF):​c.132C>G​(p.Arg44Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: BPTF NM_182641.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.711
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 17-67825856-C-G is Benign according to our data. Variant chr17-67825856-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2043706.Status of the report is criteria_provided_single_submitter, 1 stars.

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.132C>G	p.Arg44Arg	synonymous	Exon 1 of 28	NP_872579.2
	BPTF	NM_001439139.1		c.132C>G	p.Arg44Arg	synonymous	Exon 1 of 29	NP_001426068.1
	BPTF	NM_001439140.1		c.132C>G	p.Arg44Arg	synonymous	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.132C>G	p.Arg44Arg	synonymous	Exon 1 of 28	ENSP00000307208.6	Q12830-2
	BPTF	ENST00000582467.2	TSL:5	c.132C>G	p.Arg44Arg	synonymous	Exon 1 of 32	ENSP00000463776.2	J3QQK4
	BPTF	ENST00000321892.8	TSL:5	c.132C>G	p.Arg44Arg	synonymous	Exon 1 of 30	ENSP00000315454.4	Q12830-1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely 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	-0.66
CADD	Benign	9.5
DANN	Benign	0.51
PhyloP100		0.71
PromoterAI		-0.0051	Neutral

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: rs2055942962; hg19: chr17-65821972;