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GeneBe

2-237911738-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005855.4(RAMP1):c.402G>A(p.Thr134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 1,613,018 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 7 hom., cov: 33)
Exomes 𝑓: 0.013 ( 143 hom. )

Consequence

RAMP1
NM_005855.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.33
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-237911738-G-A is Benign according to our data. Variant chr2-237911738-G-A is described in ClinVar as [Benign]. Clinvar id is 789934.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=-2.33 with no splicing effect.
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 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAMP1NM_005855.4 linkuse as main transcriptc.402G>A p.Thr134= synonymous_variant 3/3 ENST00000254661.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAMP1ENST00000254661.5 linkuse as main transcriptc.402G>A p.Thr134= synonymous_variant 3/31 NM_005855.4 P1
RAMP1ENST00000403885.1 linkuse as main transcriptc.336G>A p.Thr112= synonymous_variant 3/33
RAMP1ENST00000404910.6 linkuse as main transcriptc.336G>A p.Thr112= synonymous_variant 3/32
RAMP1ENST00000409726.5 linkuse as main transcriptc.336G>A p.Thr112= synonymous_variant 4/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00813
AC:
1238
AN:
152204
Hom.:
7
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00246
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00353
Gnomad ASJ
AF:
0.0236
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00358
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0137
Gnomad OTH
AF:
0.00956
GnomAD3 exomes
AF:
0.00836
AC:
2062
AN:
246640
Hom.:
15
AF XY:
0.00863
AC XY:
1155
AN XY:
133854
show subpopulations
Gnomad AFR exome
AF:
0.00120
Gnomad AMR exome
AF:
0.00274
Gnomad ASJ exome
AF:
0.0279
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00324
Gnomad FIN exome
AF:
0.00486
Gnomad NFE exome
AF:
0.0128
Gnomad OTH exome
AF:
0.00767
GnomAD4 exome
AF:
0.0128
AC:
18722
AN:
1460696
Hom.:
143
Cov.:
31
AF XY:
0.0125
AC XY:
9116
AN XY:
726572
show subpopulations
Gnomad4 AFR exome
AF:
0.00200
Gnomad4 AMR exome
AF:
0.00301
Gnomad4 ASJ exome
AF:
0.0267
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00307
Gnomad4 FIN exome
AF:
0.00581
Gnomad4 NFE exome
AF:
0.0149
Gnomad4 OTH exome
AF:
0.0114
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00813
AC:
1238
AN:
152322
Hom.:
7
Cov.:
33
AF XY:
0.00709
AC XY:
528
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00245
Gnomad4 AMR
AF:
0.00353
Gnomad4 ASJ
AF:
0.0236
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00358
Gnomad4 NFE
AF:
0.0137
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.0128
Hom.:
6
Bravo
AF:
0.00814
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 testingInvitaeJan 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.22
Dann
Benign
0.72

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: rs61752232; hg19: chr2-238820380; COSMIC: COSV99615077; API