rs4739285

Variant names:

• chr8-21719673-T-C
• rs4739285
• NM_001495.5:c.795-13632A>G

Variant summary

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

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GFRA2	NM_001495.5	c.795-13632A>G		intron_variant	Intron 4 of 8	ENST00000524240.6	NP_001486.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFRA2	ENST00000524240.6	c.795-13632A>G		intron_variant	Intron 4 of 8	1	NM_001495.5	ENSP00000428518.1

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

African (AFR) AF: 0.137 AC: 5689 AN: 41522

American (AMR) AF: 0.552 AC: 8426 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1562 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3126 AN: 5158

South Asian (SAS) AF: 0.438 AC: 2108 AN: 4812

European-Finnish (FIN) AF: 0.565 AC: 5970 AN: 10566

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33882 AN: 67956

Other (OTH) AF: 0.423 AC: 890 AN: 2102

Alfa AF: 0.471 Hom.: 68928

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
PhyloP100		2.1
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: rs4739285; hg19: chr8-21577185;