rs11242417

chr5-138263645-T-G

Variant summary

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

The NM_001496.4(GFRA3):c.379+616A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,226 control chromosomes in the GnomAD database, including 1,499 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 0.13 (1499 hom., cov: 32)
• Consequence: GFRA3 NM_001496.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.848

Genes affected

GFRA3 (HGNC:4245): (GDNF family receptor alpha 3) The protein encoded by this gene is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor and a member of the GDNF receptor family. It forms a signaling receptor complex with RET tyrosine kinase receptor and binds the ligand, artemin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFRA3	NM_001496.4	c.379+616A>C		intron_variant		ENST00000274721.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFRA3	ENST00000274721.8	c.379+616A>C		intron_variant		1	NM_001496.4	P2
GFRA3	ENST00000378362.3	c.379+616A>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19122 AN: 152108 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.126 AC: 19130 AN: 152226 Hom.: 1499 Cov.: 32 AF XY: 0.125 AC XY: 9268 AN XY: 74416

Gnomad4 AFR AF: 0.0458

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.151

Alfa AF: 0.159 Hom.: 4145

Bravo AF: 0.119

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.8
Dann	Benign	0.66

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: rs11242417; hg19: chr5-137599334;