rs6084432

Variant names:

• chr20-3663006-G-A
• rs6084432
• NM_022139.4:c.46+348C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022139.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA4	NM_022139.4	MANE Select	c.46+348C>T		intron	N/A	NP_071422.1	Q9GZZ7-2
	GFRA4	NM_145762.3		c.46+348C>T		intron	N/A	NP_665705.1	Q9GZZ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA4	ENST00000290417.7	TSL:1 MANE Select	c.46+348C>T		intron	N/A	ENSP00000290417.2	Q9GZZ7-2
	GFRA4	ENST00000319242.8	TSL:1	c.46+348C>T		intron	N/A	ENSP00000313423.3	Q9GZZ7-1
	GFRA4	ENST00000477160.1	TSL:1	n.46+348C>T		intron	N/A	ENSP00000435801.1	Q9GZZ7-3

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

African (AFR) AF: 0.278 AC: 11531 AN: 41448

American (AMR) AF: 0.206 AC: 3152 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3472

East Asian (EAS) AF: 0.175 AC: 903 AN: 5174

South Asian (SAS) AF: 0.192 AC: 928 AN: 4826

European-Finnish (FIN) AF: 0.187 AC: 1978 AN: 10572

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11621 AN: 67974

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.180 Hom.: 11122

Bravo AF: 0.210

Asia WGS AF: 0.194 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.75
PhyloP100		0.58
PromoterAI		-0.013	Neutral
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: rs6084432; hg19: chr20-3643653;