17-60444192-T-C

Position:

• chr17-60444192-T-C

Variant summary

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

The ENST00000083182.8(APPBP2):​c.*3389A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 151,646 control chromosomes in the GnomAD database, including 9,368 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 0.19 (9368 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: APPBP2 ENST00000083182.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774

Genes affected

APPBP2 (HGNC:622): (amyloid beta precursor protein binding protein 2) The protein encoded by this gene interacts with microtubules and is functionally associated with beta-amyloid precursor protein transport and/or processing. The beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer's disease. The encoded protein may be involved in regulating cell death. This gene has been found to be highly expressed in breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APPBP2	NM_006380.5	c.*3389A>G		3_prime_UTR_variant	13/13	ENST00000083182.8	NP_006371.2
APPBP2	NM_001282476.2	c.*3389A>G		3_prime_UTR_variant	12/12		NP_001269405.1
APPBP2	XM_047435116.1	c.*3389A>G		3_prime_UTR_variant	13/13		XP_047291072.1
APPBP2	XM_047435118.1	c.*3389A>G		3_prime_UTR_variant	12/12		XP_047291074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APPBP2	ENST00000083182.8	c.*3389A>G		3_prime_UTR_variant	13/13	1	NM_006380.5	ENSP00000083182	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 28994 AN: 151104 Hom.: 9328 Cov.: 31

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00292

Gnomad FIN AF: 0.000580

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.00222 AC: 1 AN: 450 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 270

Gnomad4 FIN exome AF: 0.00235

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.192 AC: 29081 AN: 151196 Hom.: 9368 Cov.: 31 AF XY: 0.185 AC XY: 13626 AN XY: 73824

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.0761

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00230

Gnomad4 FIN AF: 0.000580

Gnomad4 NFE AF: 0.00293

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0324 Hom.: 1049

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.44

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: rs9893667; hg19: chr17-58521553;