chr4-41208648-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.85).
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB2	NM_004307.2	MANE Select	c.-417+5757T>C		intron	N/A	NP_004298.1
	APBB2	NM_001166050.2		c.-417+5757T>C		intron	N/A	NP_001159522.1
	APBB2	NM_001330656.2		c.-417+5757T>C		intron	N/A	NP_001317585.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBB2	ENST00000508593.6	TSL:1 MANE Select	c.-417+5757T>C		intron	N/A	ENSP00000427211.1
	APBB2	ENST00000513140.5	TSL:1	c.-417+5757T>C		intron	N/A	ENSP00000426018.1
	APBB2	ENST00000295974.12	TSL:2	c.-417+5757T>C		intron	N/A	ENSP00000295974.8

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

African (AFR) AF: 0.00609 AC: 253 AN: 41570

American (AMR) AF: 0.0234 AC: 358 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4820

European-Finnish (FIN) AF: 0.0315 AC: 334 AN: 10604

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0373 AC: 2535 AN: 68030

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

Alfa AF: 0.0337 Hom.: 144

Bravo AF: 0.0236

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		0.22
Mutation Taster		=100/0	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: rs10517001; hg19: chr4-41210665;