3-115675446-C-T

Position:

• chr3-115675446-C-T

Variant summary

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

The NM_002045.4(GAP43):​c.31-567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,790 control chromosomes in the GnomAD database, including 22,977 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 0.55 (22977 hom., cov: 30)
• Consequence: GAP43 NM_002045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAP43	NM_002045.4	c.31-567C>T		intron_variant		ENST00000305124.11
GAP43	NM_001130064.2	c.139-567C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAP43	ENST00000305124.11	c.31-567C>T		intron_variant		1	NM_002045.4	P1
GAP43	ENST00000393780.3	c.139-567C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82854 AN: 151672 Hom.: 22944 Cov.: 30

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.546 AC: 82937 AN: 151790 Hom.: 22977 Cov.: 30 AF XY: 0.551 AC XY: 40896 AN XY: 74156

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.528

Alfa AF: 0.528 Hom.: 27237

Bravo AF: 0.536

Asia WGS AF: 0.588 AC: 2048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.6
DANN	Benign	0.90

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: rs11926976; hg19: chr3-115394293;