3-57229366-G-C

Position:

• chr3-57229366-G-C

Variant summary

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

The ENST00000288266.8(APPL1):​c.54+1429G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,770 control chromosomes in the GnomAD database, including 12,661 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 0.37 (12661 hom., cov: 31)
• Consequence: APPL1 ENST00000288266.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

Genes affected

APPL1 (HGNC:24035): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APPL1	NM_012096.3	c.54+1429G>C		intron_variant		ENST00000288266.8	NP_036228.1
APPL1	XM_011533583.4	c.-51-1348G>C		intron_variant			XP_011531885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APPL1	ENST00000288266.8	c.54+1429G>C		intron_variant		1	NM_012096.3	ENSP00000288266	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56444 AN: 151650 Hom.: 12645 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.372 AC: 56475 AN: 151770 Hom.: 12661 Cov.: 31 AF XY: 0.383 AC XY: 28426 AN XY: 74132

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.381

Alfa AF: 0.383 Hom.: 1530

Bravo AF: 0.365

Asia WGS AF: 0.671 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4640525; hg19: chr3-57263394;