Variant chr2-237911738-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

RAMP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.33 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAMP1	NM_005855.4 linkuse as main transcript	c.402G>A	p.Thr134=	synonymous_variant	3/3	ENST00000254661.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAMP1	ENST00000254661.5 linkuse as main transcript	c.402G>A	p.Thr134=	synonymous_variant	3/3	1	NM_005855.4	P1
RAMP1	ENST00000403885.1 linkuse as main transcript	c.336G>A	p.Thr112=	synonymous_variant	3/3	3
RAMP1	ENST00000404910.6 linkuse as main transcript	c.336G>A	p.Thr112=	synonymous_variant	3/3	2
RAMP1	ENST00000409726.5 linkuse as main transcript	c.336G>A	p.Thr112=	synonymous_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.00813

AC:

1238

AN:

152204

Hom.:

Cov.:

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.:

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.:

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

AF:

0.00813

AC:

1238

AN:

152322

Hom.:

Cov.:

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.:

Bravo

AF:

0.00814

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over