12-56362612-A-T

Variant names:

• chr12-56362612-A-T
• rs78739461
• NM_001638.4:c.16+118T>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.16+118T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000116 in 859,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: APOF NM_001638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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 (BayesDel_noAF=-0.73).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOF	NM_001638.4	MANE Select	c.16+118T>A		intron	N/A	NP_001629.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOF	ENST00000398189.4	TSL:1 MANE Select	c.16+118T>A		intron	N/A	ENSP00000381250.3
	ENSG00000307495	ENST00000826586.1		n.327+2046A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 859430 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 439472

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20454

American (AMR) AF: 0.00 AC: 0 AN: 28010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 34166

South Asian (SAS) AF: 0.00 AC: 0 AN: 62656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3630

European-Non Finnish (NFE) AF: 0.00000166 AC: 1 AN: 603540

Other (OTH) AF: 0.00 AC: 0 AN: 39408

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		1.0
PromoterAI		0.048	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs78739461; hg19: chr12-56756396;