rs1235889

Positions:

• chr21-26181571-T-C

Variant summary

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

The ENST00000608591.5(APP-DT):​n.182+10519T>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 152,166 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 ENST00000608591.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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=-0.85).
• 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APP-DT	ENST00000608591.5	n.182+10519T>C		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000664668.1	n.1188T>C		non_coding_transcript_exon_variant	2/2
APP-DT	ENST00000609365.2	n.237+970T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0999

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.118

Alfa AF: 0.128 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1235889; hg19: chr21-27553890;