Genetic Variant ENSG00000224541:n.178-1924T>G (chr21-26173686-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000455275.1(ENSG00000224541):n.178-1924T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

ENSG00000224541
ENST00000455275.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.488

Publications

9 publications found

Variant links:

Genes affected

ENSG00000224541 (HGNC:):

ENSG00000224541 links:

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

APP-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APP-DT	NR_186395.1 link	n.186+2634T>G		intron_variant	Intron 1 of 2
APP-DT	NR_186396.1 link	n.186+2634T>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000224541	ENST00000455275.1 link	n.178-1924T>G	intron_variant	Intron 1 of 1	2
APP-DT	ENST00000608591.5 link	n.182+2634T>G	intron_variant	Intron 1 of 2	4
APP-DT	ENST00000609365.2 link	n.172+2634T>G	intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

2449

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.55

(source)

DANN

Benign

0.68

PhyloP100

-0.49

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over