chr2-237861218-G-A

Position:

• chr2-237861218-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.52+1491G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 152,132 control chromosomes in the GnomAD database, including 224 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 0.025 (224 hom., cov: 32)
• Consequence: RAMP1 NM_005855.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAMP1	NM_005855.4	c.52+1491G>A		intron_variant		ENST00000254661.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAMP1	ENST00000254661.5	c.52+1491G>A		intron_variant		1	NM_005855.4	P1
RAMP1	ENST00000403885.1	c.-15+1215G>A		intron_variant		3
RAMP1	ENST00000404910.6	c.-15+2091G>A		intron_variant		2
RAMP1	ENST00000409726.5	c.-76+1491G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3804 AN: 152012 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.0641

Gnomad FIN AF: 0.00501

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0251 AC: 3812 AN: 152132 Hom.: 224 Cov.: 32 AF XY: 0.0292 AC XY: 2169 AN XY: 74374

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.00501

Gnomad4 NFE AF: 0.00216

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0206 Hom.: 19

Bravo AF: 0.0301

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.82

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: rs3769048; hg19: chr2-238769861;