rs5085

chr1-161222721-C-G

Variant summary

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

The NM_001643.2(APOA2):c.185+197G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,150 control chromosomes in the GnomAD database, including 2,264 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 0.16 (2264 hom., cov: 31)
• Consequence: APOA2 NM_001643.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725

Genes affected

APOA2 (HGNC:601): (apolipoprotein A2) This gene encodes apolipoprotein (apo-) A-II, which is the second most abundant protein of the high density lipoprotein particles. The protein is found in plasma as a monomer, homodimer, or heterodimer with apolipoprotein D. Defects in this gene may result in apolipoprotein A-II deficiency or hypercholesterolemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA2	NM_001643.2	c.185+197G>C		intron_variant		ENST00000367990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA2	ENST00000367990.7	c.185+197G>C		intron_variant		1	NM_001643.2	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 25008 AN: 152032 Hom.: 2265 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.164 AC: 24999 AN: 152150 Hom.: 2264 Cov.: 31 AF XY: 0.164 AC XY: 12200 AN XY: 74398

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.175

Alfa AF: 0.164 Hom.: 290

Bravo AF: 0.167

Asia WGS AF: 0.246 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.7
Dann	Benign	0.75

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: rs5085; hg19: chr1-161192511; COSMIC: COSV57155114; COSMIC: COSV57155114;