rs364048

chr21-26171723-T-C

Variant summary

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

The ENST00000455275.1(ENSG00000224541):n.178-3887T>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 0.0842 in 152,248 control chromosomes in the GnomAD database, including 983 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 0.084 (983 hom., cov: 32)
• Consequence: ENST00000455275.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 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
	ENST00000455275.1	n.178-3887T>C		intron_variant, non_coding_transcript_variant		2
APP-DT	ENST00000608591.5	n.182+671T>C		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000609365.2	n.172+671T>C		intron_variant, non_coding_transcript_variant		4
APP-DT	ENST00000664668.1	n.153+671T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12802 AN: 152130 Hom.: 979 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0745

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

GnomAD4 genome AF: 0.0842 AC: 12824 AN: 152248 Hom.: 983 Cov.: 32 AF XY: 0.0859 AC XY: 6394 AN XY: 74442

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0705

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.0655

Gnomad4 NFE AF: 0.0240

Gnomad4 OTH AF: 0.0737

Alfa AF: 0.0368 Hom.: 425

Bravo AF: 0.0903

Asia WGS AF: 0.143 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.9
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs364048; hg19: chr21-27544041;