7-66130821-C-G

Variant names:

• chr7-66130821-C-G
• rs1787778670
• NM_014478.5:c.123C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014478.5(CRCP):​c.123C>G​(p.Asn41Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRCP NM_014478.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• Publications: 0 publications found

Genes affected

CRCP (HGNC:17888): (CGRP receptor component) This gene encodes a membrane protein that functions as part of a receptor complex for a small neuropeptide that increases intracellular cAMP levels. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ENSG00000249319 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014478.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRCP	NM_014478.5	MANE Select	c.123C>G	p.Asn41Lys	missense	Exon 3 of 6	NP_055293.1	O75575-1
	CRCP	NM_001142414.1		c.123+3081C>G		intron	N/A	NP_001135886.1	O75575-3
	CRCP	NM_001040647.2		c.45+3081C>G		intron	N/A	NP_001035737.1	O75575-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRCP	ENST00000395326.8	TSL:1 MANE Select	c.123C>G	p.Asn41Lys	missense	Exon 3 of 6	ENSP00000378736.3	O75575-1
	ENSG00000249319	ENST00000450043.2	TSL:5	c.678C>G	p.Asn226Lys	missense	Exon 9 of 12	ENSP00000396527.2	H7C0S8
	CRCP	ENST00000338592.5	TSL:1	c.45+3081C>G		intron	N/A	ENSP00000340044.5	O75575-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.3
PROVEAN	Benign	0.66	N
REVEL	Uncertain	0.37
Sift	Benign	0.078	T
Sift4G	Benign	0.062	T
Polyphen		1.0	D
Vest4		0.81
MutPred		0.82		Gain of methylation at N41 (P = 0.0051)
MVP		0.84
MPC		0.72
ClinPred		0.93	D
GERP RS		4.2
Varity_R		0.51
gMVP		0.64
Mutation Taster		=51/49	polymorphism

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: rs1787778670; hg19: chr7-65595808;