rs11197571

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005264.8(GFRA1):​c.433+28509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,274 control chromosomes in the GnomAD database, including 1,386 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 ( 1386 hom., cov: 33)

Consequence

GFRA1
NM_005264.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60
Variant links:
Genes affected
GFRA1 (HGNC:4243): (GDNF family receptor alpha 1) This gene encodes a member of the glial cell line-derived neurotrophic factor receptor (GDNFR) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature receptor. 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. This receptor is a glycosylphosphatidylinositol (GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for Hirschsprung disease. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GFRA1NM_005264.8 linkuse as main transcriptc.433+28509T>C intron_variant ENST00000355422.11 NP_005255.1 P56159-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GFRA1ENST00000355422.11 linkuse as main transcriptc.433+28509T>C intron_variant 5 NM_005264.8 ENSP00000347591.6 P56159-1

Frequencies

GnomAD3 genomes
AF:
0.133
AC:
20207
AN:
152156
Hom.:
1380
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.117
Gnomad AMI
AF:
0.147
Gnomad AMR
AF:
0.112
Gnomad ASJ
AF:
0.162
Gnomad EAS
AF:
0.0599
Gnomad SAS
AF:
0.0751
Gnomad FIN
AF:
0.126
Gnomad MID
AF:
0.104
Gnomad NFE
AF:
0.156
Gnomad OTH
AF:
0.142
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.133
AC:
20236
AN:
152274
Hom.:
1386
Cov.:
33
AF XY:
0.130
AC XY:
9656
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.117
Gnomad4 AMR
AF:
0.111
Gnomad4 ASJ
AF:
0.162
Gnomad4 EAS
AF:
0.0597
Gnomad4 SAS
AF:
0.0748
Gnomad4 FIN
AF:
0.126
Gnomad4 NFE
AF:
0.156
Gnomad4 OTH
AF:
0.142
Alfa
AF:
0.150
Hom.:
2349
Bravo
AF:
0.129
Asia WGS
AF:
0.0770
AC:
267
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
6.2
DANN
Benign
0.61

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11197571; hg19: chr10-117942634; API