rs2156079

Positions:

• chr21-26176012-G-A

Variant summary

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

The ENST00000608591.5(APP-DT):​n.182+4960G>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 0.297 in 152,064 control chromosomes in the GnomAD database, including 6,992 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 0.30 (6992 hom., cov: 33)
• Consequence: APP-DT ENST00000608591.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 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
APP-DT	ENST00000608591.5	n.182+4960G>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000609365.2	n.173-4525G>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000664668.1	n.154-4525G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45172 AN: 151944 Hom.: 6985 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.297 AC: 45207 AN: 152064 Hom.: 6992 Cov.: 33 AF XY: 0.290 AC XY: 21562 AN XY: 74346

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.296

Alfa AF: 0.287 Hom.: 8159

Bravo AF: 0.311

Asia WGS AF: 0.165 AC: 572 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2156079; hg19: chr21-27548330;