rs1080519

Variant names:

• chr2-237907559-C-T
• rs1080519
• NM_005855.4:c.192-3969C>T

Variant summary

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

The NM_005855.4(RAMP1):​c.192-3969C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 149,250 control chromosomes in the GnomAD database, including 3,938 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 0.23 (3938 hom., cov: 32)
• Consequence: RAMP1 NM_005855.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 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.192-3969C>T		intron	N/A	NP_005846.1
	RAMP1	NM_001308353.2		c.126-3969C>T		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.192-3969C>T		intron	N/A	ENSP00000254661.4
	RAMP1	ENST00000403885.1	TSL:3	c.126-3969C>T		intron	N/A	ENSP00000386046.1
	RAMP1	ENST00000404910.6	TSL:2	c.126-3969C>T		intron	N/A	ENSP00000384688.2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34357 AN: 149136 Hom.: 3933 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.230 AC: 34392 AN: 149250 Hom.: 3938 Cov.: 32 AF XY: 0.235 AC XY: 17069 AN XY: 72706

African (AFR) AF: 0.212 AC: 8642 AN: 40702

American (AMR) AF: 0.225 AC: 3339 AN: 14820

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 737 AN: 3424

East Asian (EAS) AF: 0.177 AC: 891 AN: 5036

South Asian (SAS) AF: 0.344 AC: 1622 AN: 4716

European-Finnish (FIN) AF: 0.243 AC: 2453 AN: 10082

Middle Eastern (MID) AF: 0.219 AC: 63 AN: 288

European-Non Finnish (NFE) AF: 0.239 AC: 16034 AN: 67208

Other (OTH) AF: 0.219 AC: 453 AN: 2070

Alfa AF: 0.233 Hom.: 11596

Bravo AF: 0.221

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.73
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1080519; hg19: chr2-238816201;