chr2-237907946-T-G

Variant names:

• chr2-237907946-T-G
• rs10199956
• NM_005855.4:c.192-3582T>G

Variant summary

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

The NM_005855.4(RAMP1):​c.192-3582T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,112 control chromosomes in the GnomAD database, including 19,725 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 0.50 (19725 hom., cov: 33)
• Consequence: RAMP1 NM_005855.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAMP1	NM_005855.4	c.192-3582T>G		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.192-3582T>G		intron_variant	Intron 2 of 2	1	NM_005855.4	ENSP00000254661.4
RAMP1	ENST00000403885.1	c.126-3582T>G		intron_variant	Intron 2 of 2	3		ENSP00000386046.1
RAMP1	ENST00000404910.6	c.126-3582T>G		intron_variant	Intron 2 of 2	2		ENSP00000384688.2
RAMP1	ENST00000409726.5	c.126-3582T>G		intron_variant	Intron 3 of 3	3		ENSP00000386720.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76214 AN: 151994 Hom.: 19711 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.501 AC: 76240 AN: 152112 Hom.: 19725 Cov.: 33 AF XY: 0.498 AC XY: 37057 AN XY: 74382

African (AFR) AF: 0.363 AC: 15044 AN: 41486

American (AMR) AF: 0.573 AC: 8759 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1850 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3564 AN: 5184

South Asian (SAS) AF: 0.483 AC: 2328 AN: 4824

European-Finnish (FIN) AF: 0.510 AC: 5397 AN: 10574

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37594 AN: 67984

Other (OTH) AF: 0.519 AC: 1097 AN: 2114

Alfa AF: 0.530 Hom.: 14669

Bravo AF: 0.501

Asia WGS AF: 0.553 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		-0.19
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: rs10199956; hg19: chr2-238816588;