rs1045219936

Variant names:

• chr17-60479191-C-T
• rs1045219936
• NM_006380.5:c.460G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-60479191-C-T
• chr17-60479191-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006380.5(APPBP2):​c.460G>A​(p.Asp154Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: APPBP2 NM_006380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12416139).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APPBP2	NM_006380.5	MANE Select	c.460G>A	p.Asp154Asn	missense	Exon 4 of 13	NP_006371.2
	APPBP2	NM_001282476.2		c.247G>A	p.Asp83Asn	missense	Exon 3 of 12	NP_001269405.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APPBP2	ENST00000083182.8	TSL:1 MANE Select	c.460G>A	p.Asp154Asn	missense	Exon 4 of 13	ENSP00000083182.3	Q92624
	APPBP2	ENST00000589341.5	TSL:1	n.*185G>A		non_coding_transcript_exon	Exon 3 of 12	ENSP00000467025.1	K7ENN3
	APPBP2	ENST00000589341.5	TSL:1	n.*185G>A		3_prime_UTR	Exon 3 of 12	ENSP00000467025.1	K7ENN3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461556 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111854

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.099
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.55	N
PhyloP100		4.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.24
Sift	Benign	0.74	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.44		Loss of helix (P = 0.079)
MVP		0.45
MPC		0.83
ClinPred		0.90	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.16
Mutation Taster		=82/18	polymorphism

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: rs1045219936; hg19: chr17-58556552;