rs1080519

Positions:

• chr2-237907559-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254661.5(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 ENST00000254661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMP1	NM_005855.4	c.192-3969C>T		intron_variant		ENST00000254661.5	NP_005846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAMP1	ENST00000254661.5	c.192-3969C>T		intron_variant		1	NM_005855.4	ENSP00000254661	P1
RAMP1	ENST00000403885.1	c.126-3969C>T		intron_variant		3		ENSP00000386046
RAMP1	ENST00000404910.6	c.126-3969C>T		intron_variant		2		ENSP00000384688
RAMP1	ENST00000409726.5	c.126-3969C>T		intron_variant		3		ENSP00000386720

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

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.219

Alfa AF: 0.235 Hom.: 7946

Bravo AF: 0.221

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs1080519; hg19: chr2-238816201;