rs1555693714

Variant names:

• chr17-67975933-A-G
• rs1555693714
• NM_182641.4:c.8701A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-67975933-A-G
• chr17-67975933-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182641.4(BPTF):​c.8701A>G​(p.Lys2901Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BPTF NM_182641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.21
• 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: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000279880 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPTF	NM_182641.4	MANE Select	c.8701A>G	p.Lys2901Glu	missense	Exon 27 of 28	NP_872579.2
	BPTF	NM_001439139.1		c.8890A>G	p.Lys2964Glu	missense	Exon 28 of 29	NP_001426068.1
	BPTF	NM_001439140.1		c.8824A>G	p.Lys2942Glu	missense	Exon 30 of 31	NP_001426069.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPTF	ENST00000306378.11	TSL:1 MANE Select	c.8701A>G	p.Lys2901Glu	missense	Exon 27 of 28	ENSP00000307208.6
	BPTF	ENST00000342579.8	TSL:1	c.8515A>G	p.Lys2839Glu	missense	Exon 30 of 31	ENSP00000343837.5
	BPTF	ENST00000424123.7	TSL:1	c.8233A>G	p.Lys2745Glu	missense	Exon 29 of 30	ENSP00000388405.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.2
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MVP		0.77
MPC		2.6
ClinPred		0.99	D
GERP RS		5.8
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.81
gMVP		0.80

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: rs1555693714; hg19: chr17-65972049;