chr6-54870585-C-T

Variant names:

• chr6-54870585-C-T
• rs73742854
• NM_001010872.3:c.339C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.436
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010872.3. 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
	FAM83B	NM_001010872.3	MANE Select	c.339C>T	p.Pro113Pro	synonymous	Exon 2 of 5	NP_001010872.1	Q5T0W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83B	ENST00000306858.8	TSL:1 MANE Select	c.339C>T	p.Pro113Pro	synonymous	Exon 2 of 5	ENSP00000304078.7	Q5T0W9

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4017 AN: 151910 Hom.: 199 Cov.: 32

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

GnomAD2 exomes AF: 0.00763 AC: 1914 AN: 250976 AF XY: 0.00594

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 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.: 34 AF XY: 0.00285 AC XY: 2073 AN XY: 727204

African (AFR) AF: 0.0899 AC: 3009 AN: 33474

American (AMR) AF: 0.00718 AC: 321 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000823 AC: 71 AN: 86258

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53418

Middle Eastern (MID) AF: 0.0106 AC: 61 AN: 5768

European-Non Finnish (NFE) AF: 0.000701 AC: 779 AN: 1111960

Other (OTH) AF: 0.00773 AC: 467 AN: 60396

GnomAD4 genome AF: 0.0266 AC: 4044 AN: 152028 Hom.: 204 Cov.: 32 AF XY: 0.0263 AC XY: 1956 AN XY: 74312

African (AFR) AF: 0.0898 AC: 3722 AN: 41440

American (AMR) AF: 0.0139 AC: 213 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000824 AC: 56 AN: 67996

Other (OTH) AF: 0.0218 AC: 46 AN: 2110

Alfa AF: 0.0135 Hom.: 57

Bravo AF: 0.0305

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00136

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73742854; hg19: chr6-54735383;