4-41208648-A-G

Variant names:

• chr4-41208648-A-G
• rs10517001
• NM_004307.2:c.-417+5757T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004307.2(APBB2):​c.-417+5757T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 152,302 control chromosomes in the GnomAD database, including 61 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 0.025 (61 hom., cov: 33)
• Consequence: APBB2 NM_004307.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0247 (3758/152302) while in subpopulation NFE AF= 0.0373 (2535/68030). AF 95% confidence interval is 0.0361. There are 61 homozygotes in gnomad4. There are 1825 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB2	NM_004307.2	c.-417+5757T>C		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+5757T>C		intron_variant	Intron 1 of 17	1	NM_004307.2	ENSP00000427211.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3761 AN: 152184 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.00610

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0259

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

GnomAD4 genome AF: 0.0247 AC: 3758 AN: 152302 Hom.: 61 Cov.: 33 AF XY: 0.0245 AC XY: 1825 AN XY: 74462

Gnomad4 AFR AF: 0.00609

Gnomad4 AMR AF: 0.0234

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0256 Hom.: 18

Bravo AF: 0.0236

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.55

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: rs10517001; hg19: chr4-41210665;