NM_014478.5:c.73G>A

Variant names:

• chr7-66130771-G-A
• rs764188906
• NM_014478.5:c.73G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014478.5(CRCP):​c.73G>A​(p.Glu25Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRCP NM_014478.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27582133).

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.73G>A	p.Glu25Lys	missense	Exon 3 of 6	NP_055293.1	O75575-1
	CRCP	NM_001142414.1		c.123+3031G>A		intron	N/A	NP_001135886.1	O75575-3
	CRCP	NM_001040647.2		c.45+3031G>A		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.73G>A	p.Glu25Lys	missense	Exon 3 of 6	ENSP00000378736.3	O75575-1
	ENSG00000249319	ENST00000450043.2	TSL:5	c.628G>A	p.Glu210Lys	missense	Exon 9 of 12	ENSP00000396527.2	H7C0S8
	CRCP	ENST00000338592.5	TSL:1	c.45+3031G>A		intron	N/A	ENSP00000340044.5	O75575-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250898 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.87e-7 AC: 1 AN: 1456386 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 724808

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33342

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107862

Other (OTH) AF: 0.0000166 AC: 1 AN: 60156

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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	Benign	0.17
PhyloP100		5.0
Varity_R		0.12
gMVP		0.34
Mutation Taster		=72/28	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs764188906; hg19: chr7-65595758;