11-117309175-C-T

Variant names:

• chr11-117309175-C-T
• rs676134
• NM_012104.6:c.261+6360G>A

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+6360G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,956 control chromosomes in the GnomAD database, including 22,145 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 0.52 (22145 hom., cov: 31)
• Consequence: BACE1 NM_012104.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACE1	NM_012104.6	c.261+6360G>A		intron_variant	Intron 1 of 8	ENST00000313005.11	NP_036236.1
BACE1	NM_138972.4	c.261+6360G>A		intron_variant	Intron 1 of 8		NP_620428.1
BACE1	NM_138971.4	c.261+6360G>A		intron_variant	Intron 1 of 8		NP_620427.1
BACE1	NM_138973.4	c.261+6360G>A		intron_variant	Intron 1 of 8		NP_620429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BACE1	ENST00000313005.11	c.261+6360G>A		intron_variant	Intron 1 of 8	1	NM_012104.6	ENSP00000318585.6

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79093 AN: 151838 Hom.: 22128 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.521 AC: 79155 AN: 151956 Hom.: 22145 Cov.: 31 AF XY: 0.525 AC XY: 38979 AN XY: 74286

African (AFR) AF: 0.712 AC: 29486 AN: 41422

American (AMR) AF: 0.556 AC: 8484 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1545 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3657 AN: 5166

South Asian (SAS) AF: 0.632 AC: 3051 AN: 4828

European-Finnish (FIN) AF: 0.378 AC: 3988 AN: 10552

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27166 AN: 67946

Other (OTH) AF: 0.516 AC: 1088 AN: 2110

Alfa AF: 0.447 Hom.: 27391

Bravo AF: 0.539

Asia WGS AF: 0.682 AC: 2370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.27
PhyloP100		-0.52
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: rs676134; hg19: chr11-117179891;