2-237906610-C-T

Variant summary

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

The NM_005855.4(RAMP1):c.192-4918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,684 control chromosomes in the GnomAD database, including 20,080 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 0.51 (20080 hom., cov: 30)
• Consequence: RAMP1 NM_005855.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAMP1	NM_005855.4	c.192-4918C>T		intron_variant		ENST00000254661.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAMP1	ENST00000254661.5	c.192-4918C>T		intron_variant		1	NM_005855.4	P1
RAMP1	ENST00000403885.1	c.126-4918C>T		intron_variant		3
RAMP1	ENST00000404910.6	c.126-4918C>T		intron_variant		2
RAMP1	ENST00000409726.5	c.126-4918C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77216 AN: 151564 Hom.: 20064 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.509 AC: 77247 AN: 151684 Hom.: 20080 Cov.: 30 AF XY: 0.506 AC XY: 37497 AN XY: 74078

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.525

Alfa AF: 0.538 Hom.: 10885

Bravo AF: 0.510

Asia WGS AF: 0.552 AC: 1920 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	1.1
Dann	Benign	0.48

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: rs895572; hg19: chr2-238815252;