chr2-237881216-C-A

Variant names:

• chr2-237881216-C-A
• rs7557078
• NM_005855.4:c.191+3854C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005855.4(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 NM_005855.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAMP1	NM_005855.4	c.191+3854C>A		intron_variant	Intron 2 of 2	ENST00000254661.5	NP_005846.1

Ensembl

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

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

African (AFR) AF: 0.368 AC: 15254 AN: 41484

American (AMR) AF: 0.185 AC: 2832 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1589 AN: 5178

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4820

European-Finnish (FIN) AF: 0.218 AC: 2311 AN: 10596

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13610 AN: 68016

Other (OTH) AF: 0.260 AC: 548 AN: 2108

Alfa AF: 0.213 Hom.: 3736

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
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7557078; hg19: chr2-238789858;