Genetic Variant FCHSD1:c.828+81A>G (chr5-141647317-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033449.3(FCHSD1):c.828+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,561,704 control chromosomes in the GnomAD database, including 41,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5430 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36359 hom. )

Consequence

FCHSD1
NM_033449.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

18 publications found

Variant links:

Genes affected

FCHSD1 (HGNC:25463): (FCH and double SH3 domains 1) Predicted to enable lipid binding activity. Predicted to be involved in neuromuscular synaptic transmission and positive regulation of actin filament polymerization. Predicted to be located in cell projection and perikaryon. Predicted to be active in neuromuscular junction and recycling endosome. Predicted to colocalize with cuticular plate. [provided by Alliance of Genome Resources, Apr 2022]

FCHSD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033449.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHSD1	NM_033449.3	MANE Select	c.828+81A>G		intron	N/A	NP_258260.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FCHSD1	ENST00000435817.7	TSL:1 MANE Select	c.828+81A>G	intron	N/A	ENSP00000399259.2
FCHSD1	ENST00000522783.5	TSL:5	c.822+81A>G	intron	N/A	ENSP00000428677.1
FCHSD1	ENST00000522126.5	TSL:2	n.600+81A>G	intron	N/A	ENSP00000427796.1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38417

AN:

151916

Hom.:

5431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.00947

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.248

GnomAD4 exome

AF:

0.222

AC:

312635

AN:

1409670

Hom.:

36359

Cov.:

AF XY:

0.220

AC XY:

153113

AN XY:

695422

show subpopulations

African (AFR)

AF:

0.365

AC:

11643

AN:

31928

American (AMR)

AF:

0.144

AC:

5397

AN:

37404

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7114

AN:

24382

East Asian (EAS)

AF:

0.00535

AC:

203

AN:

37952

South Asian (SAS)

AF:

0.150

AC:

12078

AN:

80616

European-Finnish (FIN)

AF:

0.183

AC:

9374

AN:

51298

Middle Eastern (MID)

AF:

0.301

AC:

1565

AN:

5196

European-Non Finnish (NFE)

AF:

0.233

AC:

252117

AN:

1082668

Other (OTH)

AF:

0.226

AC:

13144

AN:

58226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

13059

26117

39176

52234

65293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8584

17168

25752

34336

42920

<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:

0.253

AC:

38435

AN:

152034

Hom.:

5430

Cov.:

AF XY:

0.246

AC XY:

18283

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.359

AC:

14883

AN:

41450

American (AMR)

AF:

0.207

AC:

3158

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1017

AN:

3468

East Asian (EAS)

AF:

0.00949

AC:

AN:

5164

South Asian (SAS)

AF:

0.140

AC:

673

AN:

4820

European-Finnish (FIN)

AF:

0.182

AC:

1919

AN:

10564

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15917

AN:

67964

Other (OTH)

AF:

0.246

AC:

520

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1456

2912

4369

5825

7281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.241

Hom.:

7997

Bravo

AF:

0.261

Asia WGS

AF:

0.0930

AC:

324

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.30

(source)

DANN

Benign

0.75

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(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