2-237907236-T-C

Variant names:

• chr2-237907236-T-C
• rs1584243
• NM_005855.4:c.192-4292T>C

Variant summary

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

The NM_005855.4(RAMP1):​c.192-4292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,146 control chromosomes in the GnomAD database, including 58,885 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 0.88 (58885 hom., cov: 31)
• Consequence: RAMP1 NM_005855.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005855.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMP1	NM_005855.4	MANE Select	c.192-4292T>C		intron	N/A	NP_005846.1
	RAMP1	NM_001308353.2		c.126-4292T>C		intron	N/A	NP_001295282.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAMP1	ENST00000254661.5	TSL:1 MANE Select	c.192-4292T>C		intron	N/A	ENSP00000254661.4
	RAMP1	ENST00000403885.1	TSL:3	c.126-4292T>C		intron	N/A	ENSP00000386046.1
	RAMP1	ENST00000404910.6	TSL:2	c.126-4292T>C		intron	N/A	ENSP00000384688.2

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133602 AN: 152028 Hom.: 58812 Cov.: 31

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.879 AC: 133732 AN: 152146 Hom.: 58885 Cov.: 31 AF XY: 0.876 AC XY: 65130 AN XY: 74372

African (AFR) AF: 0.925 AC: 38397 AN: 41524

American (AMR) AF: 0.899 AC: 13733 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2970 AN: 3468

East Asian (EAS) AF: 0.909 AC: 4713 AN: 5186

South Asian (SAS) AF: 0.855 AC: 4118 AN: 4814

European-Finnish (FIN) AF: 0.802 AC: 8467 AN: 10552

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58555 AN: 68002

Other (OTH) AF: 0.868 AC: 1834 AN: 2114

Alfa AF: 0.865 Hom.: 91006

Bravo AF: 0.888

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.70
PhyloP100		0.20
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: rs1584243; hg19: chr2-238815878;