8-123181283-T-C

Variant names:

• chr8-123181283-T-C
• rs16898095
• ENST00000518448.5:c.-831-743T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518448.5(FAM83A):​c.-831-743T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,140 control chromosomes in the GnomAD database, including 1,062 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 0.11 (1062 hom., cov: 32)
• Consequence: FAM83A ENST00000518448.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.699
• Publications: 7 publications found

Genes affected

FAM83A (HGNC:28210): (family with sequence similarity 83 member A) Enables identical protein binding activity; phosphatidylinositol 3-kinase regulatory subunit binding activity; and protein kinase binding activity. Involved in cell population proliferation and epidermal growth factor receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM83A-AS2 (HGNC:56225): (FAM83A antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518448.5. 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
	FAM83A-AS2	NR_189631.1		n.1132A>G		non_coding_transcript_exon	Exon 2 of 2
	FAM83A	NM_032899.6		c.-831-743T>C		intron	N/A	NP_116288.2
	FAM83A	NM_207006.3		c.-831-743T>C		intron	N/A	NP_996889.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83A	ENST00000518448.5	TSL:1	c.-831-743T>C		intron	N/A	ENSP00000428876.1
	FAM83A	ENST00000536633.2	TSL:2	c.-831-743T>C		intron	N/A	ENSP00000445218.1
	FAM83A	ENST00000520541.5	TSL:5	n.356+1054T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16815 AN: 152022 Hom.: 1053 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00994

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0923

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16850 AN: 152140 Hom.: 1062 Cov.: 32 AF XY: 0.109 AC XY: 8095 AN XY: 74380

African (AFR) AF: 0.177 AC: 7349 AN: 41488

American (AMR) AF: 0.0742 AC: 1135 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00995 AC: 48 AN: 4824

European-Finnish (FIN) AF: 0.137 AC: 1444 AN: 10574

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6358 AN: 67988

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.0969 Hom.: 1868

Bravo AF: 0.110

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.7
DANN	Benign	0.31
PhyloP100		0.70
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: rs16898095; hg19: chr8-124193523;