Variant 14-54522509-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006568.3(CGRRF1):c.160A>G(p.Thr54Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CGRRF1
NM_006568.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.558

Variant links:

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]

CGRRF1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058469504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGRRF1	NM_006568.3 linkuse as main transcript	c.160A>G	p.Thr54Ala	missense_variant	2/6	ENST00000216420.12	NP_006559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGRRF1	ENST00000216420.12 linkuse as main transcript	c.160A>G	p.Thr54Ala	missense_variant	2/6	1	NM_006568.3	ENSP00000216420	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247536

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457702

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000455

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.160A>G (p.T54A) alteration is located in exon 2 (coding exon 2) of the CGRRF1 gene. This alteration results from a A to G substitution at nucleotide position 160, causing the threonine (T) at amino acid position 54 to be replaced by an alanine (A). 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

0.059

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.0034

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.98

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.034

Sift

Benign

0.56

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.25

MutPred

0.25

Gain of catalytic residue at R55 (P = 0.0428);Gain of catalytic residue at R55 (P = 0.0428);

MVP

0.092

MPC

0.081

ClinPred

0.011

GERP RS

0.87

Varity_R

0.018

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over