rs4739285

chr8-21719673-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001495.5(GFRA2):c.795-13632A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,048 control chromosomes in the GnomAD database, including 15,132 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 0.41 (15132 hom., cov: 32)
• Consequence: GFRA2 NM_001495.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

Genes affected

GFRA2 (HGNC:4244): (GDNF family receptor alpha 2) Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This encoded protein acts preferentially as a receptor for NTN compared to its other family member, GDNF family receptor alpha 1. This gene is a candidate gene for RET-associated diseases. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFRA2	NM_001495.5	c.795-13632A>G		intron_variant		ENST00000524240.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFRA2	ENST00000524240.6	c.795-13632A>G		intron_variant		1	NM_001495.5	P1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62070 AN: 151930 Hom.: 15129 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.408 AC: 62084 AN: 152048 Hom.: 15132 Cov.: 32 AF XY: 0.414 AC XY: 30744 AN XY: 74298

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.423

Alfa AF: 0.483 Hom.: 34702

Bravo AF: 0.399

Asia WGS AF: 0.461 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	22
Dann	Benign	0.79

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: rs4739285; hg19: chr8-21577185;