11-117313198-T-C

Variant names:

• chr11-117313198-T-C
• rs477036
• NM_012104.6:c.261+2337A>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+2337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,016 control chromosomes in the GnomAD database, including 19,494 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 0.50 (19494 hom., cov: 32)
• Consequence: BACE1 NM_012104.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACE1	NM_012104.6	c.261+2337A>G		intron_variant	Intron 1 of 8	ENST00000313005.11	NP_036236.1
BACE1	NM_138972.4	c.261+2337A>G		intron_variant	Intron 1 of 8		NP_620428.1
BACE1	NM_138971.4	c.261+2337A>G		intron_variant	Intron 1 of 8		NP_620427.1
BACE1	NM_138973.4	c.261+2337A>G		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+2337A>G		intron_variant	Intron 1 of 8	1	NM_012104.6	ENSP00000318585.6

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76008 AN: 151896 Hom.: 19486 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.500 AC: 76060 AN: 152016 Hom.: 19494 Cov.: 32 AF XY: 0.504 AC XY: 37430 AN XY: 74300

African (AFR) AF: 0.499 AC: 20674 AN: 41438

American (AMR) AF: 0.579 AC: 8846 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1806 AN: 3466

East Asian (EAS) AF: 0.797 AC: 4115 AN: 5160

South Asian (SAS) AF: 0.635 AC: 3058 AN: 4814

European-Finnish (FIN) AF: 0.439 AC: 4640 AN: 10564

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.458 AC: 31146 AN: 67988

Other (OTH) AF: 0.515 AC: 1088 AN: 2112

Alfa AF: 0.471 Hom.: 4893

Bravo AF: 0.509

Asia WGS AF: 0.695 AC: 2415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		-0.72
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: rs477036; hg19: chr11-117183914;