rs137875206
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005855.4(RAMP1):c.367A>C(p.Ile123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I123V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
RAMP1
NM_005855.4 missense
NM_005855.4 missense
Scores
1
4
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.483
Genes affected
RAMP1 (HGNC:9843): (receptor activity modifying protein 1) The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N terminus and a cytoplasmic C terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin-gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In the presence of this (RAMP1) protein, CRLR functions as a CGRP receptor. The RAMP1 protein is involved in the terminal glycosylation, maturation, and presentation of the CGRP receptor to the cell surface. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RAMP1 | ENST00000254661.5 | c.367A>C | p.Ile123Leu | missense_variant | Exon 3 of 3 | 1 | NM_005855.4 | ENSP00000254661.4 | ||
| RAMP1 | ENST00000403885.1 | c.301A>C | p.Ile101Leu | missense_variant | Exon 3 of 3 | 3 | ENSP00000386046.1 | |||
| RAMP1 | ENST00000404910.6 | c.301A>C | p.Ile101Leu | missense_variant | Exon 3 of 3 | 2 | ENSP00000384688.2 | |||
| RAMP1 | ENST00000409726.5 | c.301A>C | p.Ile101Leu | missense_variant | Exon 4 of 4 | 3 | ENSP00000386720.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250070Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135444
GnomAD3 exomes
AF:
AC:
1
AN:
250070
Hom.:
AF XY:
AC XY:
1
AN XY:
135444
Gnomad AFR exome
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GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;.;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;M;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
0.74
.;P;.;.
Vest4
MutPred
0.66
.;Gain of catalytic residue at I123 (P = 0.0016);.;.;
MVP
MPC
0.024
ClinPred
D
GERP RS
Varity_R
gMVP
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