dbSNP rs75613762: FRG2C:c.334+93C>T (chr3-75665296-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001124759.5(FRG2C):c.334+93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.50 ( 0 hom., cov: 53)

Exomes 𝑓: 0.38 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FRG2C
NM_001124759.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.08

Publications

1 publications found

Variant links:

Genes affected

FRG2C (HGNC:33626): (FSHD region gene 2 family member C) Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FRG2C links:

ENSG00000293315 (HGNC:):

ENSG00000293315 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.06).

BP6

Variant 3-75665296-C-T is Benign according to our data. Variant chr3-75665296-C-T is described in ClinVar as Benign. ClinVar VariationId is 982117.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001124759.5. 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
	FRG2C	NM_001124759.5	MANE Select	c.334+93C>T		intron	N/A	NP_001118231.1	A6NGY1
	FRG2C	NM_001410775.1		c.331+93C>T		intron	N/A	NP_001397704.1	C9JUX3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRG2C	ENST00000308062.8	TSL:1 MANE Select	c.334+93C>T	intron	N/A	ENSP00000312299.3	A6NGY1
FRG2C	ENST00000464571.1	TSL:1	c.331+93C>T	intron	N/A	ENSP00000419432.1	C9JUX3
ENSG00000293315	ENST00000638439.2	TSL:5	n.185+4724G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

74228

AN:

148690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.498

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.500

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.377

AC:

294593

AN:

781280

Hom.:

AF XY:

0.386

AC XY:

155437

AN XY:

402946

show subpopulations

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

African (AFR)

AF:

0.400

AC:

7526

AN:

18816

American (AMR)

AF:

0.439

AC:

12154

AN:

27688

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

7979

AN:

17810

East Asian (EAS)

AF:

0.468

AC:

15746

AN:

33654

South Asian (SAS)

AF:

0.437

AC:

25832

AN:

59092

European-Finnish (FIN)

AF:

0.484

AC:

22823

AN:

47168

Middle Eastern (MID)

AF:

0.446

AC:

1822

AN:

4088

European-Non Finnish (NFE)

AF:

0.346

AC:

185431

AN:

535706

Other (OTH)

AF:

0.410

AC:

15280

AN:

37258

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.358

Heterozygous variant carriers

12975

25950

38925

51900

64875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

2874

5748

8622

11496

14370

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.499

AC:

74271

AN:

148782

Hom.:

Cov.:

AF XY:

0.499

AC XY:

36273

AN XY:

72662

show subpopulations

African (AFR)

AF:

0.498

AC:

20041

AN:

40212

American (AMR)

AF:

0.499

AC:

7494

AN:

15004

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1702

AN:

3406

East Asian (EAS)

AF:

0.500

AC:

2500

AN:

5004

South Asian (SAS)

AF:

0.499

AC:

2334

AN:

4676

European-Finnish (FIN)

AF:

0.499

AC:

5170

AN:

10364

Middle Eastern (MID)

AF:

0.500

AC:

137

AN:

274

European-Non Finnish (NFE)

AF:

0.500

AC:

33419

AN:

66892

Other (OTH)

AF:

0.500

AC:

1027

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

3752

7504

11257

15009

18761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

894

1788

2682

3576

4470

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.3

(source)

DANN

Benign

0.66

PhyloP100

-2.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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