rs4301822

Positions:

• chr12-56361274-A-G
• chr12-56361274-A-T

Variant summary

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

The NM_001638.4(APOF):​c.932T>C​(p.Ile311Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,613,896 control chromosomes in the GnomAD database, including 12,488 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (6566 hom., cov: 32)
  • Exomes 𝑓: 0.017 (5922 hom.)
• Consequence: APOF NM_001638.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

APOF (HGNC:615): (apolipoprotein F) The product of this gene is one of the minor apolipoproteins found in plasma. This protein forms complexes with lipoproteins and may be involved in transport and/or esterification of cholesterol. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.9995535E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOF	NM_001638.4	c.932T>C	p.Ile311Thr	missense_variant	2/2	ENST00000398189.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOF	ENST00000398189.4	c.932T>C	p.Ile311Thr	missense_variant	2/2	1	NM_001638.4	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24436 AN: 152090 Hom.: 6532 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.0421 AC: 10487 AN: 249188 Hom.: 2586 AF XY: 0.0325 AC XY: 4388 AN XY: 135196

Gnomad AFR exome AF: 0.572

Gnomad AMR exome AF: 0.0290

Gnomad ASJ exome AF: 0.0229

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00214

Gnomad OTH exome AF: 0.0217

GnomAD4 exome AF: 0.0173 AC: 25226 AN: 1461688 Hom.: 5922 Cov.: 31 AF XY: 0.0149 AC XY: 10842 AN XY: 727122

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.0337

Gnomad4 ASJ exome AF: 0.0215

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00123

Gnomad4 OTH exome AF: 0.0378

GnomAD4 genome AF: 0.161 AC: 24524 AN: 152208 Hom.: 6566 Cov.: 32 AF XY: 0.156 AC XY: 11600 AN XY: 74426

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.0673

Gnomad4 ASJ AF: 0.0237

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00237

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0337 Hom.: 2400

Bravo AF: 0.184

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.540 AC: 2014

ESP6500EA AF: 0.00453 AC: 37

ExAC AF: 0.0504 AC: 6090

Asia WGS AF: 0.0310 AC: 110 AN: 3478

EpiCase AF: 0.00300

EpiControl AF: 0.00379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.1
DANN	Benign	0.85
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0064	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.000050	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.020
Sift	Benign	0.068	T
Sift4G	Uncertain	0.026	D
Polyphen		0.014	B
Vest4		0.033
MPC		0.14
ClinPred		0.0084	T
GERP RS		-0.83
Varity_R		0.059
gMVP		0.12

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: rs4301822; hg19: chr12-56755058; COSMIC: COSV58474970; COSMIC: COSV58474970;