3-115668163-T-C

Variant summary

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

The NM_002045.4(GAP43):c.31-7850T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,918 control chromosomes in the GnomAD database, including 18,832 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 0.49 (18832 hom., cov: 31)
• Consequence: GAP43 NM_002045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

GAP43 (HGNC:4140): (growth associated protein 43) The protein encoded by this gene has been termed a 'growth' or 'plasticity' protein because it is expressed at high levels in neuronal growth cones during development and axonal regeneration. This protein is considered a crucial component of an effective regenerative response in the nervous system. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAP43	NM_002045.4	c.31-7850T>C		intron_variant		ENST00000305124.11
GAP43	NM_001130064.2	c.138+4247T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAP43	ENST00000305124.11	c.31-7850T>C		intron_variant		1	NM_002045.4	P1
GAP43	ENST00000393780.3	c.138+4247T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74208 AN: 151800 Hom.: 18804 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.489 AC: 74283 AN: 151918 Hom.: 18832 Cov.: 31 AF XY: 0.496 AC XY: 36803 AN XY: 74262

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.471

Alfa AF: 0.501 Hom.: 4787

Bravo AF: 0.472

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.45
Dann	Benign	0.74

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: rs4831199; hg19: chr3-115387010;