Genetic Variant NM_006568.3:c.987G>A (chr14-54538371-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006568.3(CGRRF1):c.987G>A(p.Pro329Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,606,648 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 64 hom. )

Consequence

CGRRF1
NM_006568.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.537

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 14-54538371-G-A is Benign according to our data. Variant chr14-54538371-G-A is described in ClinVar as Benign. ClinVar VariationId is 718035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.537 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006568.3. 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
	CGRRF1	NM_006568.3	MANE Select	c.987G>A	p.Pro329Pro	synonymous	Exon 6 of 6	NP_006559.1	Q99675

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CGRRF1	ENST00000216420.12	TSL:1 MANE Select	c.987G>A	p.Pro329Pro	synonymous	Exon 6 of 6	ENSP00000216420.7	Q99675
CGRRF1	ENST00000908184.1		c.1122G>A	p.Pro374Pro	synonymous	Exon 8 of 8	ENSP00000578243.1
CGRRF1	ENST00000908185.1		c.1080G>A	p.Pro360Pro	synonymous	Exon 7 of 7	ENSP00000578244.1

Frequencies

GnomAD3 genomes

AF:

0.00485

AC:

738

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00569

AC:

1422

AN:

249726

AF XY:

0.00579

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.000804

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0413

Gnomad NFE exome

AF:

0.00370

Gnomad OTH exome

AF:

0.00511

GnomAD4 exome

AF:

0.00426

AC:

6189

AN:

1454336

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

3055

AN XY:

721912

show subpopulations

African (AFR)

AF:

0.000570

AC:

AN:

33340

American (AMR)

AF:

0.00175

AC:

AN:

44514

Ashkenazi Jewish (ASJ)

AF:

0.000692

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.000918

AC:

AN:

86030

European-Finnish (FIN)

AF:

0.0382

AC:

2034

AN:

53278

Middle Eastern (MID)

AF:

0.00922

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00328

AC:

3629

AN:

1105870

Other (OTH)

AF:

0.00464

AC:

279

AN:

60072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

310

621

931

1242

1552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

134

268

402

536

670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00485

AC:

738

AN:

152312

Hom.:

Cov.:

AF XY:

0.00617

AC XY:

460

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41576

American (AMR)

AF:

0.00242

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0377

AC:

400

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00348

AC:

237

AN:

68020

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00195

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00362

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.9

(source)

DANN

Benign

0.48

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over