rs2156079

Variant names:

• chr21-26176012-G-A
• rs2156079
• ENST00000717650.1:n.685G>A

Variant summary

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

The ENST00000717650.1(APP-DT):​n.685G>A variant causes a non coding transcript exon 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 ENST00000717650.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 5 publications found

Genes affected

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

ENSG00000224541 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
APP-DT	NR_186395.1	n.186+4960G>A		intron_variant	Intron 1 of 2
APP-DT	NR_186396.1	n.187-4525G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APP-DT	ENST00000717650.1	n.685G>A		non_coding_transcript_exon_variant	Exon 3 of 3
APP-DT	ENST00000608591.5	n.182+4960G>A		intron_variant	Intron 1 of 2	4
APP-DT	ENST00000609365.2	n.173-4525G>A		intron_variant	Intron 1 of 3	4

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

African (AFR) AF: 0.382 AC: 15833 AN: 41466

American (AMR) AF: 0.302 AC: 4609 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3466

East Asian (EAS) AF: 0.110 AC: 569 AN: 5190

South Asian (SAS) AF: 0.145 AC: 699 AN: 4820

European-Finnish (FIN) AF: 0.187 AC: 1973 AN: 10558

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19606 AN: 67978

Other (OTH) AF: 0.296 AC: 623 AN: 2108

Alfa AF: 0.291 Hom.: 10700

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
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs2156079; hg19: chr21-27548330;