chr12-56361764-C-T

Variant names:

• chr12-56361764-C-T
• rs768502018
• NM_001638.4:c.442G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001638.4(APOF):​c.442G>A​(p.Ala148Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,610,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: APOF NM_001638.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.276
• Publications: 0 publications found

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]

ENSG00000307495 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048349142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001638.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOF	NM_001638.4	MANE Select	c.442G>A	p.Ala148Thr	missense	Exon 2 of 2	NP_001629.1	Q13790

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOF	ENST00000398189.4	TSL:1 MANE Select	c.442G>A	p.Ala148Thr	missense	Exon 2 of 2	ENSP00000381250.3	Q13790
	APOF	ENST00000887741.1		c.481G>A	p.Ala161Thr	missense	Exon 2 of 2	ENSP00000557800.1
	APOF	ENST00000887742.1		c.427G>A	p.Ala143Thr	missense	Exon 2 of 2	ENSP00000557801.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000539 AC: 13 AN: 241182 AF XY: 0.0000535

Gnomad AFR exome AF: 0.0000676

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000261 AC: 38 AN: 1457786 Hom.: 0 Cov.: 31 AF XY: 0.0000262 AC XY: 19 AN XY: 724856

African (AFR) AF: 0.0000299 AC: 1 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 43890

Ashkenazi Jewish (ASJ) AF: 0.000999 AC: 26 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110130

Other (OTH) AF: 0.0000830 AC: 5 AN: 60268

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000203 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000579 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.28
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.027
Sift	Benign	0.041	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.25	B
Vest4		0.083
MutPred		0.30		Gain of catalytic residue at A148 (P = 0.1333)
MVP		0.55
MPC		0.28
ClinPred		0.13	T
GERP RS		3.5
Varity_R		0.10
gMVP		0.18
Mutation Taster		=82/18	polymorphism

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: rs768502018; hg19: chr12-56755548;