chr10-43080177-T-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_020975.6(RET):c.73+2846T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,230 control chromosomes in the GnomAD database, including 48,801 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 0.79 ( 48801 hom., cov: 35)
Consequence
RET
NM_020975.6 intron
NM_020975.6 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.641
Publications
3 publications found
Genes affected
RET (HGNC:9967): (ret proto-oncogene) This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]
RET Gene-Disease associations (from GenCC):
- familial medullary thyroid carcinomaInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
- multiple endocrine neoplasia type 2AInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P
- multiple endocrine neoplasia type 2BInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
- pheochromocytomaInheritance: AD Classification: DEFINITIVE Submitted by: G2P
- Hirschsprung disease, susceptibility to, 1Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Haddad syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Hirschsprung diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- renal agenesis, unilateralInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- bilateral renal agenesisInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- renal agenesisInheritance: AR Classification: LIMITED Submitted by: G2P
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.73+2846T>G | intron_variant | Intron 1 of 19 | ENST00000355710.8 | NP_066124.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.792 AC: 120434AN: 152112Hom.: 48734 Cov.: 35 show subpopulations
GnomAD3 genomes
AF:
AC:
120434
AN:
152112
Hom.:
Cov.:
35
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.792 AC: 120568AN: 152230Hom.: 48801 Cov.: 35 AF XY: 0.784 AC XY: 58362AN XY: 74412 show subpopulations
GnomAD4 genome
AF:
AC:
120568
AN:
152230
Hom.:
Cov.:
35
AF XY:
AC XY:
58362
AN XY:
74412
show subpopulations
African (AFR)
AF:
AC:
39612
AN:
41582
American (AMR)
AF:
AC:
11722
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
AC:
2428
AN:
3470
East Asian (EAS)
AF:
AC:
2770
AN:
5156
South Asian (SAS)
AF:
AC:
3434
AN:
4828
European-Finnish (FIN)
AF:
AC:
6762
AN:
10590
Middle Eastern (MID)
AF:
AC:
210
AN:
294
European-Non Finnish (NFE)
AF:
AC:
51227
AN:
67984
Other (OTH)
AF:
AC:
1643
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1258
2516
3774
5032
6290
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
864
1728
2592
3456
4320
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
2263
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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