chr22-40040969-G-C

Variant names:

• chr22-40040969-G-C
• rs11704416
• NM_138435.4:c.*11404G>C

Variant summary

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

The NM_138435.4(FAM83F):​c.*11404G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,198 control chromosomes in the GnomAD database, including 3,407 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 (3405 hom., cov: 32)
  • Exomes 𝑓: 0.30 (2 hom.)
• Consequence: FAM83F NM_138435.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 28 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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83F	NM_138435.4	c.*11404G>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000333407.11	NP_612444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83F	ENST00000333407.11	c.*11404G>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_138435.4	ENSP00000330432.5

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31263 AN: 152060 Hom.: 3405 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.300 AC: 6 AN: 20 Hom.: 2 Cov.: 0 AF XY: 0.222 AC XY: 4 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 6 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.206 AC: 31279 AN: 152178 Hom.: 3405 Cov.: 32 AF XY: 0.202 AC XY: 15028 AN XY: 74394

African (AFR) AF: 0.250 AC: 10390 AN: 41512

American (AMR) AF: 0.140 AC: 2135 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 691 AN: 3470

East Asian (EAS) AF: 0.0290 AC: 150 AN: 5176

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4824

European-Finnish (FIN) AF: 0.191 AC: 2027 AN: 10594

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13722 AN: 67990

Other (OTH) AF: 0.189 AC: 400 AN: 2116

Alfa AF: 0.200 Hom.: 394

Bravo AF: 0.199

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.5
DANN	Benign	0.73
PhyloP100		0.30
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: rs11704416; hg19: chr22-40436973;