Variant 14-54531033-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006568.3(CGRRF1):c.553C>T(p.Arg185Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,608,624 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 85 hom. )

Consequence

CGRRF1
NM_006568.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006599784).

BP6

Variant 14-54531033-C-T is Benign according to our data. Variant chr14-54531033-C-T is described in ClinVar as [Benign]. Clinvar id is 710468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00748 (1138/152078) while in subpopulation AMR AF= 0.0189 (288/15268). AF 95% confidence interval is 0.0171. There are 11 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGRRF1	NM_006568.3 linkuse as main transcript	c.553C>T	p.Arg185Trp	missense_variant	4/6	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.553C>T	p.Arg185Trp	missense_variant	4/6	1	NM_006568.3	ENSP00000216420	P1

Frequencies

GnomAD3 genomes

AF:

0.00751

AC:

1141

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00213

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.00284

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00693

AC:

1703

AN:

245854

Hom.:

AF XY:

0.00732

AC XY:

973

AN XY:

132958

show subpopulations

Gnomad AFR exome

AF:

0.00218

Gnomad AMR exome

AF:

0.00911

Gnomad ASJ exome

AF:

0.000808

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.00362

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00891

AC:

12978

AN:

1456546

Hom.:

Cov.:

AF XY:

0.00886

AC XY:

6418

AN XY:

724414

show subpopulations

Gnomad4 AFR exome

AF:

0.00256

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.00104

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00298

Gnomad4 FIN exome

AF:

0.00443

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.00748

AC:

1138

AN:

152078

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

553

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00284

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00964

Hom.:

Bravo

AF:

0.00852

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0105

AC:

ExAC

AF:

0.00693

AC:

841

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.0129

EpiControl

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.076

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.99

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

REVEL

Benign

0.10

Sift

Uncertain

0.014

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.66

MVP

0.42

MPC

0.45

ClinPred

0.055

GERP RS

4.6

Varity_R

0.11

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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