chr3-195583808-G-A

Variant names:

• chr3-195583808-G-A
• rs4677695
• NM_001647.4:c.-35+70C>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.-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
• Publications: 8 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 = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOD	NM_001647.4	c.-35+70C>T		intron_variant	Intron 1 of 4	ENST00000343267.8	NP_001638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOD	ENST00000343267.8	c.-35+70C>T		intron_variant	Intron 1 of 4	1	NM_001647.4	ENSP00000345179.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.107 AC: 4432 AN: 41506

American (AMR) AF: 0.107 AC: 1634 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2164 AN: 5170

South Asian (SAS) AF: 0.278 AC: 1343 AN: 4826

European-Finnish (FIN) AF: 0.151 AC: 1600 AN: 10566

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

European-Non Finnish (NFE) AF: 0.138 AC: 9411 AN: 68010

Other (OTH) AF: 0.142 AC: 299 AN: 2106

Alfa AF: 0.141 Hom.: 4731

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
PhyloP100		-1.6
PromoterAI		-0.035	Neutral
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: rs4677695; hg19: chr3-195310679;