Genetic Variant FAM83B:p.Pro113Pro (chr6-54870585-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001010872.3(FAM83B):c.339C>T(p.Pro113Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,613,836 control chromosomes in the GnomAD database, including 378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 204 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 174 hom. )

Consequence

FAM83B
NM_001010872.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.436

Variant links:

Genes affected

FAM83B (HGNC:21357): (family with sequence similarity 83 member B) Enables epidermal growth factor receptor binding activity; phosphatidylinositol 3-kinase binding activity; and protein kinase binding activity. Involved in cell population proliferation and epidermal growth factor receptor signaling pathway. Located in cytoplasm and membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM83B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 6-54870585-C-T is Benign according to our data. Variant chr6-54870585-C-T is described in ClinVar as [Benign]. Clinvar id is 768100.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.436 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83B	NM_001010872.3 link	c.339C>T	p.Pro113Pro	synonymous_variant	Exon 2 of 5	ENST00000306858.8	NP_001010872.1	Q5T0W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83B	ENST00000306858.8 link	c.339C>T	p.Pro113Pro	synonymous_variant	Exon 2 of 5	1	NM_001010872.3	ENSP00000304078.7		Q5T0W9

Frequencies

GnomAD3 genomes

AF:

0.0264

AC:

4017

AN:

151910

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00763

AC:

1914

AN:

250976

Hom.:

AF XY:

0.00594

AC XY:

805

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.0931

Gnomad AMR exome

AF:

0.00611

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00325

AC:

4747

AN:

1461808

Hom.:

174

Cov.:

AF XY:

0.00285

AC XY:

2073

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0899

Gnomad4 AMR exome

AF:

0.00718

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000701

Gnomad4 OTH exome

AF:

0.00773

GnomAD4 genome

AF:

0.0266

AC:

4044

AN:

152028

Hom.:

204

Cov.:

AF XY:

0.0263

AC XY:

1956

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0898

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000824

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0305

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.3

DANN

Benign

0.37

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

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