chr22-40011570-C-T

Variant names:

• chr22-40011570-C-T
• rs17406434
• NM_138435.4:c.490-7598C>T

Variant summary

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

The NM_138435.4(FAM83F):​c.490-7598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,088 control chromosomes in the GnomAD database, including 4,372 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 0.21 (4372 hom., cov: 32)
• Consequence: FAM83F NM_138435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83F	NM_138435.4	c.490-7598C>T		intron_variant	Intron 1 of 4	ENST00000333407.11	NP_612444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83F	ENST00000333407.11	c.490-7598C>T		intron_variant	Intron 1 of 4	1	NM_138435.4	ENSP00000330432.5
FAM83F	ENST00000473717.1	c.-16+1446C>T		intron_variant	Intron 1 of 4	1		ENSP00000476600.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32291 AN: 151970 Hom.: 4367 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.212 AC: 32296 AN: 152088 Hom.: 4372 Cov.: 32 AF XY: 0.211 AC XY: 15676 AN XY: 74330

African (AFR) AF: 0.0600 AC: 2491 AN: 41514

American (AMR) AF: 0.175 AC: 2668 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3468

East Asian (EAS) AF: 0.148 AC: 765 AN: 5170

South Asian (SAS) AF: 0.212 AC: 1023 AN: 4816

European-Finnish (FIN) AF: 0.273 AC: 2885 AN: 10552

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20861 AN: 67966

Other (OTH) AF: 0.203 AC: 428 AN: 2110

Alfa AF: 0.273 Hom.: 10412

Bravo AF: 0.198

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.54
PhyloP100		-2.8
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: rs17406434; hg19: chr22-40407574;