Genetic Variant FAM83B:p.Ile166Ile (chr6-54926424-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001010872.3(FAM83B):c.498C>T(p.Ile166Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000488 in 1,608,150 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

FAM83B
NM_001010872.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00500

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 6-54926424-C-T is Benign according to our data. Variant chr6-54926424-C-T is described in ClinVar as [Benign]. Clinvar id is 711976.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.005 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83B	NM_001010872.3 link	c.498C>T	p.Ile166Ile	synonymous_variant	Exon 3 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.498C>T	p.Ile166Ile	synonymous_variant	Exon 3 of 5	1	NM_001010872.3	ENSP00000304078.7		Q5T0W9

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

378

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00861

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000984

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000782

AC:

196

AN:

250538

Hom.:

AF XY:

0.000539

AC XY:

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000727

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000278

AC:

405

AN:

1456146

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

161

AN XY:

724554

show subpopulations

Gnomad4 AFR exome

AF:

0.00950

Gnomad4 AMR exome

AF:

0.000942

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000902

Gnomad4 OTH exome

AF:

0.000533

GnomAD4 genome

AF:

0.00250

AC:

380

AN:

152004

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00863

Gnomad4 AMR

AF:

0.000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00309

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 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

-0.29

CADD

Benign

9.3

DANN

Benign

0.79

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