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GeneBe

5-138253842-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001496.4(GFRA3):c.948C>T(p.Cys316=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,613,866 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 58 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 54 hom. )

Consequence

GFRA3
NM_001496.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-138253842-G-A is Benign according to our data. Variant chr5-138253842-G-A is described in ClinVar as [Benign]. Clinvar id is 776066.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.062 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0149 (2264/152262) while in subpopulation AFR AF= 0.0507 (2106/41536). AF 95% confidence interval is 0.0489. There are 58 homozygotes in gnomad4. There are 1094 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 58 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GFRA3NM_001496.4 linkuse as main transcriptc.948C>T p.Cys316= synonymous_variant 6/8 ENST00000274721.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GFRA3ENST00000274721.8 linkuse as main transcriptc.948C>T p.Cys316= synonymous_variant 6/81 NM_001496.4 P2O60609-1
GFRA3ENST00000378362.3 linkuse as main transcriptc.855C>T p.Cys285= synonymous_variant 5/71 A2O60609-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0148
AC:
2259
AN:
152144
Hom.:
58
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00819
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00388
AC:
975
AN:
251358
Hom.:
29
AF XY:
0.00284
AC XY:
386
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.0516
Gnomad AMR exome
AF:
0.00292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00153
AC:
2229
AN:
1461604
Hom.:
54
Cov.:
33
AF XY:
0.00136
AC XY:
988
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.0518
Gnomad4 AMR exome
AF:
0.00376
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000684
Gnomad4 OTH exome
AF:
0.00356
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0149
AC:
2264
AN:
152262
Hom.:
58
Cov.:
32
AF XY:
0.0147
AC XY:
1094
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0507
Gnomad4 AMR
AF:
0.00818
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00804
Alfa
AF:
0.00702
Hom.:
13
Bravo
AF:
0.0175
Asia WGS
AF:
0.00462
AC:
16
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
6.6
Dann
Benign
0.51

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: rs114764339; hg19: chr5-137589531; API