4-40952255-T-C

Variant names:

• chr4-40952255-T-C
• rs6857327
• NM_004307.2:c.836-7182A>G

Variant summary

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

The NM_004307.2(APBB2):​c.836-7182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 150,824 control chromosomes in the GnomAD database, including 3,832 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 0.22 (3832 hom., cov: 29)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 1 publications found

Genes affected

APBB2 (HGNC:582): (amyloid beta precursor protein binding family B member 2) The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta (A4) precursor-like protein 2. This protein contains two phosphotyrosine binding (PTB) domains, which are thought to function in signal transduction. Polymorphisms in this gene have been associated with Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004307.2. 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
	APBB2	NM_004307.2	MANE Select	c.836-7182A>G		intron	N/A	NP_004298.1	Q92870-4
	APBB2	NM_001166050.2		c.836-7185A>G		intron	N/A	NP_001159522.1	Q92870-1
	APBB2	NM_001330656.2		c.836-7185A>G		intron	N/A	NP_001317585.1	G5E9Y1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB2	ENST00000508593.6	TSL:1 MANE Select	c.836-7182A>G		intron	N/A	ENSP00000427211.1	Q92870-4
	APBB2	ENST00000513140.5	TSL:1	c.836-7185A>G		intron	N/A	ENSP00000426018.1	Q92870-2
	APBB2	ENST00000894650.1		c.836-7182A>G		intron	N/A	ENSP00000564709.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32683 AN: 150734 Hom.: 3825 Cov.: 29

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 32714 AN: 150824 Hom.: 3832 Cov.: 29 AF XY: 0.212 AC XY: 15574 AN XY: 73544

African (AFR) AF: 0.276 AC: 11279 AN: 40932

American (AMR) AF: 0.154 AC: 2347 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 685 AN: 3468

East Asian (EAS) AF: 0.0191 AC: 98 AN: 5138

South Asian (SAS) AF: 0.140 AC: 669 AN: 4772

European-Finnish (FIN) AF: 0.184 AC: 1882 AN: 10214

Middle Eastern (MID) AF: 0.219 AC: 63 AN: 288

European-Non Finnish (NFE) AF: 0.221 AC: 15006 AN: 67820

Other (OTH) AF: 0.207 AC: 433 AN: 2090

Alfa AF: 0.201 Hom.: 1715

Bravo AF: 0.218

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.65
PhyloP100		0.15
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: rs6857327; hg19: chr4-40954272;