rs3021274

Positions:

• chr22-39999080-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138435.4(FAM83F):​c.489+3549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,112 control chromosomes in the GnomAD database, including 24,996 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 0.56 (24993 hom., cov: 33)
  • Exomes 𝑓: 0.54 (3 hom.)
• Consequence: FAM83F NM_138435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

FAM83F (HGNC:25148): (family with sequence similarity 83 member F) Predicted to enable protein kinase binding activity. Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM83F	NM_138435.4	c.489+3549T>C		intron_variant		ENST00000333407.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM83F	ENST00000333407.11	c.489+3549T>C		intron_variant		1	NM_138435.4	P1
FAM83F	ENST00000488874.1	n.516T>C		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85605 AN: 151968 Hom.: 24954 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.523

GnomAD4 exome AF: 0.542 AC: 13 AN: 24 Hom.: 3 Cov.: 0 AF XY: 0.417 AC XY: 5 AN XY: 12

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.563 AC: 85697 AN: 152088 Hom.: 24993 Cov.: 33 AF XY: 0.556 AC XY: 41343 AN XY: 74334

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.522

Alfa AF: 0.555 Hom.: 37992

Bravo AF: 0.553

Asia WGS AF: 0.449 AC: 1564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.28
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs3021274; hg19: chr22-40395084;