rs7726580

Positions:

• chr5-138272977-G-A
• chr5-138272977-G-C

Variant summary

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

The NM_001496.4(GFRA3):​c.91+1357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,042 control chromosomes in the GnomAD database, including 10,742 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 0.37 (10742 hom., cov: 31)
• Consequence: GFRA3 NM_001496.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFRA3	NM_001496.4	c.91+1357C>T		intron_variant		ENST00000274721.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFRA3	ENST00000274721.8	c.91+1357C>T		intron_variant		1	NM_001496.4	P2
GFRA3	ENST00000378362.3	c.91+1357C>T		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56038 AN: 151922 Hom.: 10722 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.369 AC: 56095 AN: 152042 Hom.: 10742 Cov.: 31 AF XY: 0.370 AC XY: 27473 AN XY: 74326

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.350

Alfa AF: 0.396 Hom.: 4154

Bravo AF: 0.365

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.056
DANN	Benign	0.18

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: rs7726580; hg19: chr5-137608666;