rs2280520

Variant names:

• chr3-195579012-G-A
• rs2280520
• NM_001647.4:c.123+327C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001647.4(APOD):​c.123+327C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,134 control chromosomes in the GnomAD database, including 1,843 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 0.14 (1843 hom., cov: 31)
• Consequence: APOD NM_001647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 2 publications found

Genes affected

APOD (HGNC:612): (apolipoprotein D) This gene encodes a component of high density lipoprotein that has no marked similarity to other apolipoprotein sequences. It has a high degree of homology to plasma retinol-binding protein and other members of the alpha 2 microglobulin protein superfamily of carrier proteins, also known as lipocalins. This glycoprotein is closely associated with the enzyme lecithin:cholesterol acyltransferase - an enzyme involved in lipoprotein metabolism. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOD	NM_001647.4	c.123+327C>T		intron_variant	Intron 2 of 4	ENST00000343267.8	NP_001638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOD	ENST00000343267.8	c.123+327C>T		intron_variant	Intron 2 of 4	1	NM_001647.4	ENSP00000345179.3

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21136 AN: 152016 Hom.: 1840 Cov.: 31

Gnomad AFR AF: 0.0940

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.139 AC: 21143 AN: 152134 Hom.: 1843 Cov.: 31 AF XY: 0.143 AC XY: 10627 AN XY: 74366

African (AFR) AF: 0.0941 AC: 3905 AN: 41520

American (AMR) AF: 0.104 AC: 1597 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2123 AN: 5140

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4824

European-Finnish (FIN) AF: 0.151 AC: 1601 AN: 10598

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9488 AN: 67968

Other (OTH) AF: 0.140 AC: 297 AN: 2114

Alfa AF: 0.145 Hom.: 698

Bravo AF: 0.136

Asia WGS AF: 0.309 AC: 1074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.49
PhyloP100		0.21
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: rs2280520; hg19: chr3-195305883;