chr21-26171301-C-T

Position:

• chr21-26171301-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The ENST00000455275.1(ENSG00000224541):​n.178-4309C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000966 in 152,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.00097 (0 hom., cov: 32)
• Consequence: ENSG00000224541 ENST00000455275.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.28

Genes affected

ENSG00000224541 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 21-26171301-C-T is Benign according to our data. Variant chr21-26171301-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1117397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APP-DT	NR_186395.1	n.186+249C>T		intron_variant
APP-DT	NR_186396.1	n.186+249C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000224541	ENST00000455275.1	n.178-4309C>T		intron_variant		2
APP-DT	ENST00000608591.5	n.182+249C>T		intron_variant		4
APP-DT	ENST00000609365.2	n.172+249C>T		intron_variant		4
APP-DT	ENST00000664668.1	n.153+249C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.000967 AC: 147 AN: 152006 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.000957

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

GnomAD4 genome AF: 0.000966 AC: 147 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.000901 AC XY: 67 AN XY: 74384

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00111

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

APP: BS1 -

APP-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 11, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Alzheimer disease Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs187510057; hg19: chr21-27543619;