3-115668163-T-C

Variant names:

• chr3-115668163-T-C
• rs4831199
• NM_002045.4:c.31-7850T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GAP43	NM_002045.4	c.31-7850T>C		intron_variant	Intron 1 of 2	ENST00000305124.11	NP_002036.1
GAP43	NM_001130064.2	c.138+4247T>C		intron_variant	Intron 2 of 3		NP_001123536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAP43	ENST00000305124.11	c.31-7850T>C		intron_variant	Intron 1 of 2	1	NM_002045.4	ENSP00000305010.7
GAP43	ENST00000393780.3	c.138+4247T>C		intron_variant	Intron 2 of 3	1		ENSP00000377372.3

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

African (AFR) AF: 0.399 AC: 16534 AN: 41424

American (AMR) AF: 0.470 AC: 7179 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3452 AN: 5140

South Asian (SAS) AF: 0.423 AC: 2038 AN: 4822

European-Finnish (FIN) AF: 0.687 AC: 7249 AN: 10548

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34838 AN: 67944

Other (OTH) AF: 0.471 AC: 992 AN: 2106

Alfa AF: 0.500 Hom.: 7439

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
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4831199; hg19: chr3-115387010;