rs363973

Variant names:

• chr21-26172668-C-A
• rs363973
• ENST00000455275.1:n.178-2942C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000455275.1(ENSG00000224541):​n.178-2942C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 152,082 control chromosomes in the GnomAD database, including 824 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 0.079 (824 hom., cov: 33)
• Consequence: ENSG00000224541 ENST00000455275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 1 publications found

Genes affected

ENSG00000224541 (HGNC:):

APP-DT (HGNC:55075): (APP divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• 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 rank	MANE	Protein	UniProt
APP-DT	NR_186395.1	n.186+1616C>A		intron_variant	Intron 1 of 2
APP-DT	NR_186396.1	n.186+1616C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000224541	ENST00000455275.1	n.178-2942C>A		intron_variant	Intron 1 of 1	2
APP-DT	ENST00000608591.5	n.182+1616C>A		intron_variant	Intron 1 of 2	4
APP-DT	ENST00000609365.2	n.172+1616C>A		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 11993 AN: 151964 Hom.: 820 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0780

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0239

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0790 AC: 12010 AN: 152082 Hom.: 824 Cov.: 33 AF XY: 0.0806 AC XY: 5995 AN XY: 74344

African (AFR) AF: 0.171 AC: 7089 AN: 41440

American (AMR) AF: 0.0670 AC: 1024 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1045 AN: 5150

South Asian (SAS) AF: 0.0775 AC: 374 AN: 4828

European-Finnish (FIN) AF: 0.0651 AC: 690 AN: 10594

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0239 AC: 1623 AN: 68000

Other (OTH) AF: 0.0699 AC: 148 AN: 2116

Alfa AF: 0.0627 Hom.: 72

Bravo AF: 0.0847

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.23
DANN	Benign	0.31
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs363973; hg19: chr21-27544986;