dbSNP rs3769048: RAMP1:c.52+1491G>A (chr2-237861218-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005855.4(RAMP1):c.52+1491G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 152,132 control chromosomes in the GnomAD database, including 224 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 0.025 ( 224 hom., cov: 32)

Consequence

RAMP1
NM_005855.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.589

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAMP1	NM_005855.4 link	c.52+1491G>A		intron_variant	Intron 1 of 2	ENST00000254661.5	NP_005846.1	O60894

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAMP1	ENST00000254661.5 link	c.52+1491G>A	intron_variant	Intron 1 of 2	1	NM_005855.4	ENSP00000254661.4	O60894
RAMP1	ENST00000403885.1 link	c.-15+1215G>A	intron_variant	Intron 1 of 2	3		ENSP00000386046.1	E9PC20
RAMP1	ENST00000404910.6 link	c.-15+2091G>A	intron_variant	Intron 1 of 2	2		ENSP00000384688.2	E9PC20
RAMP1	ENST00000409726.5 link	c.-76+1491G>A	intron_variant	Intron 1 of 3	3		ENSP00000386720.1	E9PC20

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3804

AN:

152012

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0764

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.0641

Gnomad FIN

AF:

0.00501

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.0191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0251

AC:

3812

AN:

152132

Hom.:

224

Cov.:

AF XY:

0.0292

AC XY:

2169

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0204

AC:

847

AN:

41492

American (AMR)

AF:

0.0764

AC:

1168

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3472

East Asian (EAS)

AF:

0.227

AC:

1175

AN:

5176

South Asian (SAS)

AF:

0.0648

AC:

311

AN:

4802

European-Finnish (FIN)

AF:

0.00501

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00216

AC:

147

AN:

67998

Other (OTH)

AF:

0.0203

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

156

313

469

626

782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0206

Hom.:

Bravo

AF:

0.0301

Asia WGS

AF:

0.154

AC:

537

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.7

(source)

DANN

Benign

0.82

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over