rs438031

Variant names:

• chr21-26173686-T-C
• rs438031
• ENST00000455275.1:n.178-1924T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-26173686-T-C
• chr21-26173686-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000455275.1(ENSG00000224541):​n.178-1924T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,246 control chromosomes in the GnomAD database, including 1,448 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 (1448 hom., cov: 32)
• Consequence: ENSG00000224541 ENST00000455275.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 9 publications found

Genes affected

ENSG00000224541 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000455275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APP-DT	NR_186395.1		n.186+2634T>C		intron	N/A
	APP-DT	NR_186396.1		n.186+2634T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000224541	ENST00000455275.1	TSL:2	n.178-1924T>C		intron	N/A
	APP-DT	ENST00000608591.5	TSL:4	n.182+2634T>C		intron	N/A
	APP-DT	ENST00000609365.2	TSL:4	n.172+2634T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18235 AN: 152126 Hom.: 1445 Cov.: 32

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.165

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: 18245 AN: 152246 Hom.: 1448 Cov.: 32 AF XY: 0.126 AC XY: 9383 AN XY: 74408

African (AFR) AF: 0.0335 AC: 1391 AN: 41578

American (AMR) AF: 0.173 AC: 2641 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3472

East Asian (EAS) AF: 0.100 AC: 519 AN: 5174

South Asian (SAS) AF: 0.165 AC: 799 AN: 4828

European-Finnish (FIN) AF: 0.220 AC: 2320 AN: 10564

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9643 AN: 68022

Other (OTH) AF: 0.118 AC: 249 AN: 2116

Alfa AF: 0.132 Hom.: 2449

Bravo AF: 0.114

Asia WGS AF: 0.105 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.65
PhyloP100		-0.49

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs438031;

hg19: chr21-27546004;