rs363973

Positions:

• chr21-26172668-C-A

Variant summary

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

The ENST00000455275.1(ENSG00000224541):​n.178-2942C>A variant causes a intron, non coding transcript 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: ENST00000455275.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

Genes affected

(HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000455275.1	n.178-2942C>A		intron_variant, non_coding_transcript_variant		2
APP-DT	ENST00000608591.5	n.182+1616C>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000609365.2	n.172+1616C>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000664668.1	n.153+1616C>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.0775

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0239

Gnomad4 OTH AF: 0.0699

Alfa AF: 0.0582 Hom.: 63

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs363973; hg19: chr21-27544986;