rs463946

Positions:

• chr21-26173869-C-G
• chr21-26173869-C-A
• chr21-26173869-C-T

Variant summary

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

The ENST00000455275.1(ENSG00000224541):​n.178-1741C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,248 control chromosomes in the GnomAD database, including 1,005 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 0.085 (1005 hom., cov: 33)
• Consequence: ENSG00000224541 ENST00000455275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

Genes affected

ENSG00000224541 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APP-DT	NR_186395.1	n.186+2817C>G		intron_variant
APP-DT	NR_186396.1	n.186+2817C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000224541	ENST00000455275.1	n.178-1741C>G		intron_variant		2
APP-DT	ENST00000608591.5	n.182+2817C>G		intron_variant		4
APP-DT	ENST00000609365.2	n.172+2817C>G		intron_variant		4
APP-DT	ENST00000664668.1	n.153+2817C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12958 AN: 152128 Hom.: 999 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0751

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

GnomAD4 genome AF: 0.0853 AC: 12988 AN: 152248 Hom.: 1005 Cov.: 33 AF XY: 0.0868 AC XY: 6464 AN XY: 74438

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0653

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0182 Hom.: 7

Bravo AF: 0.0915

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.4
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs463946; hg19: chr21-27546187;