Genetic Variant ENST00000616721.6:c.11447C>T (chr19-39872380-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000616721.6(FCGBP):c.11447C>T(p.Ala3816Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,365,360 control chromosomes in the GnomAD database, including 31,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3816T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.21 ( 3758 hom., cov: 33)

Exomes 𝑓: 0.21 ( 28226 hom. )

Consequence

FCGBP
ENST00000616721.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.818

Publications

27 publications found

Variant links:

Genes affected

FCGBP (HGNC:13572): (Fc gamma binding protein) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

FCGBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.095).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGBP	NM_003890.3 link	c.11486C>T	p.Ala3829Val	missense_variant	Exon 32 of 36		NP_003881.2	Q9Y6R7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGBP	ENST00000616721.6 link	c.11447C>T	p.Ala3816Val	missense_variant	Exon 24 of 28	1		ENSP00000481056.3		A0A087WXI2

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32016

AN:

152010

Hom.:

3758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.188

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.235

AC:

56626

AN:

241416

AF XY:

0.238

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.268

Gnomad EAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.209

AC:

253925

AN:

1213232

Hom.:

28226

Cov.:

AF XY:

0.213

AC XY:

128085

AN XY:

601236

show subpopulations

African (AFR)

AF:

0.178

AC:

4676

AN:

26270

American (AMR)

AF:

0.160

AC:

5907

AN:

36920

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

4433

AN:

16862

East Asian (EAS)

AF:

0.552

AC:

9182

AN:

16638

South Asian (SAS)

AF:

0.274

AC:

22803

AN:

83140

European-Finnish (FIN)

AF:

0.179

AC:

5740

AN:

32016

Middle Eastern (MID)

AF:

0.243

AC:

1085

AN:

4464

European-Non Finnish (NFE)

AF:

0.199

AC:

190065

AN:

953058

Other (OTH)

AF:

0.229

AC:

10034

AN:

43864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

12312

24623

36935

49246

61558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7714

15428

23142

30856

38570

<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:

0.211

AC:

32030

AN:

152128

Hom.:

3758

Cov.:

AF XY:

0.212

AC XY:

15735

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.187

AC:

7781

AN:

41510

American (AMR)

AF:

0.189

AC:

2886

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

920

AN:

3470

East Asian (EAS)

AF:

0.555

AC:

2858

AN:

5148

South Asian (SAS)

AF:

0.292

AC:

1411

AN:

4828

European-Finnish (FIN)

AF:

0.164

AC:

1738

AN:

10604

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13704

AN:

67958

Other (OTH)

AF:

0.224

AC:

473

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1295

2590

3884

5179

6474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.213

Hom.:

9010

Bravo

AF:

0.212

Asia WGS

AF:

0.390

AC:

1351

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.23

(source)

DANN

Benign

0.45

PhyloP100

-0.82

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over