rs6084432

chr20-3663006-G-A

Variant summary

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

The NM_022139.4(GFRA4):c.46+348C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,080 control chromosomes in the GnomAD database, including 3,464 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 0.21 (3464 hom., cov: 32)
• Consequence: GFRA4 NM_022139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576

Genes affected

GFRA4 (HGNC:13821): (GDNF family receptor alpha 4) The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for persephin, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for RET-associated diseases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFRA4	NM_022139.4	c.46+348C>T		intron_variant		ENST00000290417.7
GFRA4	NM_145762.3	c.46+348C>T		intron_variant
GFRA4	XM_005260793.2	c.46+348C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFRA4	ENST00000290417.7	c.46+348C>T		intron_variant		1	NM_022139.4	P1
GFRA4	ENST00000319242.8	c.46+348C>T		intron_variant		1
GFRA4	ENST00000477160.1	c.46+348C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31369 AN: 151962 Hom.: 3464 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.206 AC: 31373 AN: 152080 Hom.: 3464 Cov.: 32 AF XY: 0.205 AC XY: 15266 AN XY: 74350

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.221

Alfa AF: 0.175 Hom.: 4992

Bravo AF: 0.210

Asia WGS AF: 0.194 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.8
Dann	Benign	0.75

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: rs6084432; hg19: chr20-3643653;