21-26173686-T-C

Position:

• chr21-26173686-T-C

Variant summary

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

The ENST00000455275.1(ENSG00000224541):​n.178-1924T>C 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 0.12 in 152,246 control chromosomes in the GnomAD database, including 1,448 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 0.12 (1448 hom., cov: 32)
• Consequence: ENST00000455275.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000455275.1	n.178-1924T>C		intron_variant, non_coding_transcript_variant		2
APP-DT	ENST00000608591.5	n.182+2634T>C		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000609365.2	n.172+2634T>C		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000664668.1	n.153+2634T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18235 AN: 152126 Hom.: 1445 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.120 AC: 18245 AN: 152246 Hom.: 1448 Cov.: 32 AF XY: 0.126 AC XY: 9383 AN XY: 74408

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.118

Alfa AF: 0.134 Hom.: 2001

Bravo AF: 0.114

Asia WGS AF: 0.105 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs438031; hg19: chr21-27546004;