chr5-138263645-T-G

Variant names:

• chr5-138263645-T-G
• rs11242417
• NM_001496.4:c.379+616A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001496.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA3	NM_001496.4	MANE Select	c.379+616A>C		intron	N/A	NP_001487.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA3	ENST00000274721.8	TSL:1 MANE Select	c.379+616A>C		intron	N/A	ENSP00000274721.3
	GFRA3	ENST00000378362.3	TSL:1	c.379+616A>C		intron	N/A	ENSP00000367613.3
	GFRA3	ENST00000714689.1		c.379+616A>C		intron	N/A	ENSP00000519918.1

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

African (AFR) AF: 0.0458 AC: 1903 AN: 41558

American (AMR) AF: 0.147 AC: 2252 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5168

South Asian (SAS) AF: 0.0955 AC: 461 AN: 4826

European-Finnish (FIN) AF: 0.191 AC: 2022 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11221 AN: 68004

Other (OTH) AF: 0.151 AC: 319 AN: 2116

Alfa AF: 0.152 Hom.: 8335

Bravo AF: 0.119

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.66
PhyloP100		0.85
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: rs11242417; hg19: chr5-137599334;