rs4677695

Positions:

• chr3-195583808-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.-35+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,150 control chromosomes in the GnomAD database, including 1,916 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 (1916 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APOD NM_001647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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 = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOD	NM_001647.4	c.-35+70C>T		intron_variant		ENST00000343267.8	NP_001638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOD	ENST00000343267.8	c.-35+70C>T		intron_variant		1	NM_001647.4	ENSP00000345179	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21662 AN: 152032 Hom.: 1910 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.138

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.142 AC: 21672 AN: 152150 Hom.: 1916 Cov.: 32 AF XY: 0.146 AC XY: 10854 AN XY: 74374

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.142

Alfa AF: 0.145 Hom.: 3003

Bravo AF: 0.139

Asia WGS AF: 0.311 AC: 1080 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	0.13
DANN	Benign	0.60

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: rs4677695; hg19: chr3-195310679;