17-60444192-T-C

Variant names:

• chr17-60444192-T-C
• rs9893667
• NM_006380.5:c.*3389A>G

Variant summary

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

The NM_006380.5(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 NM_006380.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006380.5. 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
	APPBP2	NM_006380.5	MANE Select	c.*3389A>G		3_prime_UTR	Exon 13 of 13	NP_006371.2
	APPBP2	NM_001282476.2		c.*3389A>G		3_prime_UTR	Exon 12 of 12	NP_001269405.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APPBP2	ENST00000083182.8	TSL:1 MANE Select	c.*3389A>G		3_prime_UTR	Exon 13 of 13	ENSP00000083182.3

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00235 AC: 1 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.667 AC: 27381 AN: 41068

American (AMR) AF: 0.0761 AC: 1155 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5150

South Asian (SAS) AF: 0.00230 AC: 11 AN: 4780

European-Finnish (FIN) AF: 0.000580 AC: 6 AN: 10344

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.00293 AC: 199 AN: 67904

Other (OTH) AF: 0.133 AC: 279 AN: 2094

Alfa AF: 0.0641 Hom.: 3359

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.2
DANN	Benign	0.44
PhyloP100		0.77
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: rs9893667; hg19: chr17-58521553;