chr11-117308287-T-C

Variant names:

• chr11-117308287-T-C
• rs551662
• NM_012104.6:c.261+7248A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012104.6. 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
	BACE1	NM_012104.6	MANE Select	c.261+7248A>G		intron	N/A	NP_036236.1	P56817-1
	BACE1	NM_138972.4		c.261+7248A>G		intron	N/A	NP_620428.1	P56817-2
	BACE1	NM_138971.4		c.261+7248A>G		intron	N/A	NP_620427.1	P56817-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BACE1	ENST00000313005.11	TSL:1 MANE Select	c.261+7248A>G		intron	N/A	ENSP00000318585.6	P56817-1
	BACE1	ENST00000513780.5	TSL:1	c.261+7248A>G		intron	N/A	ENSP00000424536.1	P56817-2
	BACE1	ENST00000445823.6	TSL:1	c.261+7248A>G		intron	N/A	ENSP00000403685.2	P56817-3

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

African (AFR) AF: 0.0150 AC: 622 AN: 41580

American (AMR) AF: 0.0655 AC: 1002 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4828

European-Finnish (FIN) AF: 0.0564 AC: 599 AN: 10622

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0933 AC: 6343 AN: 68018

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.0749 Hom.: 318

Bravo AF: 0.0623

Asia WGS AF: 0.0200 AC: 70 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	2.0
DANN	Benign	0.63
PhyloP100		-0.56
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: rs551662; hg19: chr11-117179003;