4-41205322-C-T

Variant names:

• chr4-41205322-C-T
• rs17443381
• NM_004307.2:c.-417+9083G>A

Variant summary

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

The NM_004307.2(APBB2):​c.-417+9083G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,158 control chromosomes in the GnomAD database, including 699 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 0.080 (699 hom., cov: 32)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 2 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-417+9083G>A		intron_variant	Intron 1 of 17	ENST00000508593.6	NP_004298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB2	ENST00000508593.6	c.-417+9083G>A		intron_variant	Intron 1 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12220 AN: 152040 Hom.: 699 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.0976

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.0815

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

GnomAD4 genome AF: 0.0803 AC: 12218 AN: 152158 Hom.: 699 Cov.: 32 AF XY: 0.0782 AC XY: 5819 AN XY: 74376

African (AFR) AF: 0.0223 AC: 928 AN: 41536

American (AMR) AF: 0.0784 AC: 1198 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 338 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1188 AN: 10562

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8136 AN: 68008

Other (OTH) AF: 0.0806 AC: 170 AN: 2108

Alfa AF: 0.102 Hom.: 1491

Bravo AF: 0.0749

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.011
DANN	Benign	0.91
PhyloP100		-2.7
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: rs17443381; hg19: chr4-41207339;