7-66134349-G-A

Position:

• chr7-66134349-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014478.5(CRCP):​c.214G>A​(p.Ala72Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRCP NM_014478.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3112395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRCP	NM_014478.5	c.214G>A	p.Ala72Thr	missense_variant	4/6	ENST00000395326.8	NP_055293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRCP	ENST00000395326.8	c.214G>A	p.Ala72Thr	missense_variant	4/6	1	NM_014478.5	ENSP00000378736.3
ENSG00000249319	ENST00000450043.2	c.769G>A	p.Ala257Thr	missense_variant	10/12	5		ENSP00000396527.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458656 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725808

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.214G>A (p.A72T) alteration is located in exon 4 (coding exon 4) of the CRCP gene. This alteration results from a G to A substitution at nucleotide position 214, causing the alanine (A) at amino acid position 72 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	.;T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.67	.;N;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.6	.;D;D;D
REVEL	Benign	0.072
Sift	Benign	0.10	.;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.29, 0.20	.;B;.;B
Vest4		0.28, 0.30, 0.29
MutPred		0.41		.;Gain of glycosylation at A72 (P = 0.0581);.;.;
MVP		0.16
MPC		0.46
ClinPred		0.97	D
GERP RS		4.1
Varity_R		0.25
gMVP		0.26

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: rs1787906597; hg19: chr7-65599336;