14-54522496-G-C

Variant names:

• chr14-54522496-G-C
• NM_006568.3:c.147G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006568.3(CGRRF1):​c.147G>C​(p.Glu49Asp) 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 benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CGRRF1 NM_006568.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.281

Genes affected

CGRRF1 (HGNC:15528): (cell growth regulator with ring finger domain 1) Predicted to enable metal ion binding activity. Predicted to be involved in negative regulation of cell growth. Located in endoplasmic reticulum and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19972238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGRRF1	NM_006568.3	c.147G>C	p.Glu49Asp	missense_variant	Exon 2 of 6	ENST00000216420.12	NP_006559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGRRF1	ENST00000216420.12	c.147G>C	p.Glu49Asp	missense_variant	Exon 2 of 6	1	NM_006568.3	ENSP00000216420.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.147G>C (p.E49D) alteration is located in exon 2 (coding exon 2) of the CGRRF1 gene. This alteration results from a G to C substitution at nucleotide position 147, causing the glutamic acid (E) at amino acid position 49 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0075	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.97	N;N
REVEL	Benign	0.16
Sift	Benign	0.098	T;D
Sift4G	Uncertain	0.060	T;T
Polyphen		0.99	D;.
Vest4		0.66
MutPred		0.20		Gain of MoRF binding (P = 0.1163);Gain of MoRF binding (P = 0.1163);
MVP		0.33
MPC		0.44
ClinPred		0.83	D
GERP RS		2.2
Varity_R		0.11
gMVP		0.50

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-54989214;