chr2-237872208-G-A

Position:

• chr2-237872208-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMP1	NM_005855.4	c.53-5016G>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.53-5016G>A		intron_variant		1	NM_005855.4	ENSP00000254661.4
RAMP1	ENST00000403885.1	c.-14-5016G>A		intron_variant		3		ENSP00000386046.1
RAMP1	ENST00000404910.6	c.-14-5016G>A		intron_variant		2		ENSP00000384688.2
RAMP1	ENST00000409726.5	c.-75-2437G>A		intron_variant		3		ENSP00000386720.1

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

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.371

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.94

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: rs302678; hg19: chr2-238780851;