rs2280520

Positions:

• chr3-195579012-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
APOD	NM_001647.4	c.123+327C>T		intron_variant		ENST00000343267.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOD	ENST00000343267.8	c.123+327C>T		intron_variant		1	NM_001647.4	P1

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

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.140

Alfa AF: 0.134 Hom.: 304

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

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: rs2280520; hg19: chr3-195305883;