rs364091

Positions:

• chr21-26173102-G-A
• chr21-26173102-G-C

Variant summary

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

The ENST00000455275.1(ENSG00000224541):​n.178-2508G>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 0.0465 in 151,284 control chromosomes in the GnomAD database, including 277 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 0.047 (277 hom., cov: 32)
• Consequence: ENST00000455275.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 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
	ENST00000455275.1	n.178-2508G>A		intron_variant, non_coding_transcript_variant		2
APP-DT	ENST00000608591.5	n.182+2050G>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000609365.2	n.172+2050G>A		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000664668.1	n.153+2050G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7028 AN: 151152 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.0776

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.0132

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0465 AC: 7037 AN: 151284 Hom.: 277 Cov.: 32 AF XY: 0.0495 AC XY: 3659 AN XY: 73886

Gnomad4 AFR AF: 0.0580

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.0770

Gnomad4 FIN AF: 0.0653

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0357 Hom.: 19

Bravo AF: 0.0476

Asia WGS AF: 0.138 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.5
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs364091; hg19: chr21-27545420;