3-195573805-A-G

Variant names:

• chr3-195573805-A-G
• rs1568566
• NM_001647.4:c.245+45T>C

Variant summary

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

The NM_001647.4(APOD):​c.245+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,603,624 control chromosomes in the GnomAD database, including 564,026 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 0.87 (57590 hom., cov: 32)
  • Exomes 𝑓: 0.83 (506436 hom.)
• Consequence: APOD NM_001647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 12 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOD	NM_001647.4	c.245+45T>C		intron_variant	Intron 3 of 4	ENST00000343267.8	NP_001638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOD	ENST00000343267.8	c.245+45T>C		intron_variant	Intron 3 of 4	1	NM_001647.4	ENSP00000345179.3

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131730 AN: 152082 Hom.: 57532 Cov.: 32

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.868

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.870

GnomAD2 exomes AF: 0.830 AC: 201348 AN: 242686 AF XY: 0.823

Gnomad AFR exome AF: 0.973

Gnomad AMR exome AF: 0.758

Gnomad ASJ exome AF: 0.857

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.798

Gnomad NFE exome AF: 0.844

Gnomad OTH exome AF: 0.834

GnomAD4 exome AF: 0.833 AC: 1209441 AN: 1451424 Hom.: 506436 Cov.: 34 AF XY: 0.829 AC XY: 598247 AN XY: 721526

African (AFR) AF: 0.975 AC: 32396 AN: 33240

American (AMR) AF: 0.755 AC: 33184 AN: 43944

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 21952 AN: 25460

East Asian (EAS) AF: 0.998 AC: 39337 AN: 39410

South Asian (SAS) AF: 0.687 AC: 57933 AN: 84372

European-Finnish (FIN) AF: 0.799 AC: 42251 AN: 52912

Middle Eastern (MID) AF: 0.848 AC: 4646 AN: 5476

European-Non Finnish (NFE) AF: 0.838 AC: 927190 AN: 1106618

Other (OTH) AF: 0.843 AC: 50552 AN: 59992

GnomAD4 genome AF: 0.866 AC: 131843 AN: 152200 Hom.: 57590 Cov.: 32 AF XY: 0.861 AC XY: 64039 AN XY: 74398

African (AFR) AF: 0.970 AC: 40291 AN: 41554

American (AMR) AF: 0.788 AC: 12035 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2979 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5149 AN: 5180

South Asian (SAS) AF: 0.691 AC: 3330 AN: 4816

European-Finnish (FIN) AF: 0.792 AC: 8373 AN: 10574

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56814 AN: 68008

Other (OTH) AF: 0.871 AC: 1840 AN: 2112

Alfa AF: 0.857 Hom.: 27738

Bravo AF: 0.877

Asia WGS AF: 0.874 AC: 3040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		1.0
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: rs1568566; hg19: chr3-195300676;