chr2-237872208-G-A

Variant names:

• chr2-237872208-G-A
• rs302678
• NM_005855.4:c.53-5016G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005855.4(RAMP1):​c.53-5016G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,108 control chromosomes in the GnomAD database, including 12,673 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 0.38 (12673 hom., cov: 32)
• Consequence: RAMP1 NM_005855.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005855.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMP1	NM_005855.4	MANE Select	c.53-5016G>A		intron	N/A	NP_005846.1
	RAMP1	NM_001308353.2		c.-75-2437G>A		intron	N/A	NP_001295282.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMP1	ENST00000254661.5	TSL:1 MANE Select	c.53-5016G>A		intron	N/A	ENSP00000254661.4
	RAMP1	ENST00000403885.1	TSL:3	c.-14-5016G>A		intron	N/A	ENSP00000386046.1
	RAMP1	ENST00000404910.6	TSL:2	c.-14-5016G>A		intron	N/A	ENSP00000384688.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57432 AN: 151988 Hom.: 12677 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.378 AC: 57423 AN: 152108 Hom.: 12673 Cov.: 32 AF XY: 0.378 AC XY: 28133 AN XY: 74348

African (AFR) AF: 0.146 AC: 6055 AN: 41538

American (AMR) AF: 0.371 AC: 5680 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1556 AN: 3464

East Asian (EAS) AF: 0.426 AC: 2196 AN: 5154

South Asian (SAS) AF: 0.306 AC: 1476 AN: 4816

European-Finnish (FIN) AF: 0.511 AC: 5412 AN: 10590

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33813 AN: 67942

Other (OTH) AF: 0.371 AC: 781 AN: 2106

Alfa AF: 0.352 Hom.: 1412

Bravo AF: 0.358

Asia WGS AF: 0.314 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.94
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs302678; hg19: chr2-238780851;