chr2-237881216-C-A

Position:

• chr2-237881216-C-A

Variant summary

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

The ENST00000254661.5(RAMP1):​c.191+3854C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,162 control chromosomes in the GnomAD database, including 5,389 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 0.25 (5389 hom., cov: 33)
• Consequence: RAMP1 ENST00000254661.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMP1	NM_005855.4	c.191+3854C>A		intron_variant		ENST00000254661.5	NP_005846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAMP1	ENST00000254661.5	c.191+3854C>A		intron_variant		1	NM_005855.4	ENSP00000254661	P1
RAMP1	ENST00000403885.1	c.125+3854C>A		intron_variant		3		ENSP00000386046
RAMP1	ENST00000404910.6	c.125+3854C>A		intron_variant		2		ENSP00000384688
RAMP1	ENST00000409726.5	c.125+3854C>A		intron_variant		3		ENSP00000386720

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38633 AN: 152042 Hom.: 5384 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.254 AC: 38666 AN: 152162 Hom.: 5389 Cov.: 33 AF XY: 0.253 AC XY: 18795 AN XY: 74378

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.260

Alfa AF: 0.214 Hom.: 2376

Bravo AF: 0.258

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs7557078; hg19: chr2-238789858;