rs4567028

Variant names:

• chr8-21722498-G-A
• rs4567028
• NM_001495.5:c.795-16457C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001495.5(GFRA2):​c.795-16457C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,112 control chromosomes in the GnomAD database, including 43,348 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 0.75 (43348 hom., cov: 32)
• Consequence: GFRA2 NM_001495.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.857
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFRA2	NM_001495.5	c.795-16457C>T		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.795-16457C>T		intron_variant	Intron 4 of 8	1	NM_001495.5	ENSP00000428518.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113244 AN: 151994 Hom.: 43317 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.745 AC: 113326 AN: 152112 Hom.: 43348 Cov.: 32 AF XY: 0.754 AC XY: 56070 AN XY: 74354

African (AFR) AF: 0.561 AC: 23265 AN: 41444

American (AMR) AF: 0.814 AC: 12444 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2525 AN: 3470

East Asian (EAS) AF: 0.809 AC: 4195 AN: 5188

South Asian (SAS) AF: 0.830 AC: 4000 AN: 4818

European-Finnish (FIN) AF: 0.911 AC: 9655 AN: 10604

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.808 AC: 54923 AN: 67990

Other (OTH) AF: 0.734 AC: 1548 AN: 2108

Alfa AF: 0.789 Hom.: 105325

Bravo AF: 0.728

Asia WGS AF: 0.797 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.1
DANN	Benign	0.45
PhyloP100		0.86
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: rs4567028; hg19: chr8-21580010;