1-161222721-C-G

Variant names:

• chr1-161222721-C-G
• rs5085
• NM_001643.2:c.185+197G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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]

APOA2 Gene-Disease associations (from GenCC):

• apolipoprotein A-II amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001643.2. 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
	APOA2	NM_001643.2	MANE Select	c.185+197G>C		intron	N/A	NP_001634.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA2	ENST00000367990.7	TSL:1 MANE Select	c.185+197G>C		intron	N/A	ENSP00000356969.3
	APOA2	ENST00000463273.6	TSL:1	c.185+197G>C		intron	N/A	ENSP00000476740.2
	APOA2	ENST00000470459.6	TSL:5	c.185+197G>C		intron	N/A	ENSP00000477031.1

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

African (AFR) AF: 0.107 AC: 4426 AN: 41504

American (AMR) AF: 0.220 AC: 3362 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 755 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1573 AN: 5168

South Asian (SAS) AF: 0.136 AC: 657 AN: 4830

European-Finnish (FIN) AF: 0.157 AC: 1663 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12000 AN: 67984

Other (OTH) AF: 0.175 AC: 369 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.7
DANN	Benign	0.75
PhyloP100		0.72
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: rs5085; hg19: chr1-161192511; COSMIC: COSV57155114; COSMIC: COSV57155114;