chr21-26174597-G-A

Position:

• chr21-26174597-G-A

Variant summary

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

The ENST00000455275.1(ENSG00000224541):​n.178-1013G>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 0.058 in 152,060 control chromosomes in the GnomAD database, including 311 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 0.058 (311 hom., cov: 32)
• Consequence: ENST00000455275.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 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.178-1013G>A		intron_variant, non_coding_transcript_variant		2
APP-DT	ENST00000608591.5	n.182+3545G>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000609365.2	n.172+3545G>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000664668.1	n.153+3545G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8819 AN: 151942 Hom.: 311 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0483

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0580 AC: 8822 AN: 152060 Hom.: 311 Cov.: 32 AF XY: 0.0566 AC XY: 4206 AN XY: 74328

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.0738

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0560 Hom.: 39

Bravo AF: 0.0625

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11911934; hg19: chr21-27546915;