rs551662

Positions:

• chr11-117308287-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012104.6(BACE1):​c.261+7248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 152,300 control chromosomes in the GnomAD database, including 462 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 0.063 (462 hom., cov: 31)
• Consequence: BACE1 NM_012104.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

Genes affected

BACE1 (HGNC:933): (beta-secretase 1) This gene encodes a member of the peptidase A1 family of aspartic proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protease. This transmembrane protease catalyzes the first step in the formation of amyloid beta peptide from amyloid precursor protein. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of human Alzheimer's disease patients. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BACE1	NM_012104.6	c.261+7248A>G		intron_variant		ENST00000313005.11	NP_036236.1
BACE1	NM_138971.4	c.261+7248A>G		intron_variant			NP_620427.1
BACE1	NM_138972.4	c.261+7248A>G		intron_variant			NP_620428.1
BACE1	NM_138973.4	c.261+7248A>G		intron_variant			NP_620429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BACE1	ENST00000313005.11	c.261+7248A>G		intron_variant		1	NM_012104.6	ENSP00000318585	P1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9644 AN: 152182 Hom.: 462 Cov.: 31

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0939

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

GnomAD4 genome AF: 0.0633 AC: 9639 AN: 152300 Hom.: 462 Cov.: 31 AF XY: 0.0621 AC XY: 4624 AN XY: 74468

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0655

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0924

Alfa AF: 0.0832 Hom.: 274

Bravo AF: 0.0623

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.63

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: rs551662; hg19: chr11-117179003;