rs1235889

Variant names:

• chr21-26181571-T-C
• rs1235889
• ENST00000664668.1:n.1188T>C

Variant summary

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

The ENST00000664668.1(APP-DT):​n.1188T>C 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 0.12 in 152,166 control chromosomes in the GnomAD database, including 1,444 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 (1444 hom., cov: 32)
• Consequence: APP-DT ENST00000664668.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APP-DT	NR_186395.1	n.186+10519T>C		intron_variant	Intron 1 of 2
APP-DT	NR_186396.1	n.251+970T>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APP-DT	ENST00000664668.1	n.1188T>C		non_coding_transcript_exon_variant	Exon 2 of 2
APP-DT	ENST00000608591.5	n.182+10519T>C		intron_variant	Intron 1 of 2	4
APP-DT	ENST00000609365.2	n.237+970T>C		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18233 AN: 152050 Hom.: 1442 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.164

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: 18240 AN: 152166 Hom.: 1444 Cov.: 32 AF XY: 0.126 AC XY: 9394 AN XY: 74386

African (AFR) AF: 0.0335 AC: 1390 AN: 41546

American (AMR) AF: 0.173 AC: 2647 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.0999 AC: 517 AN: 5176

South Asian (SAS) AF: 0.165 AC: 795 AN: 4826

European-Finnish (FIN) AF: 0.220 AC: 2323 AN: 10558

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9637 AN: 67996

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.125 Hom.: 176

Bravo AF: 0.114

Asia WGS AF: 0.104 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.78
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs1235889; hg19: chr21-27553890;