Variant chr3-195569087-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001647.4(APOD):c.383A>G(p.Tyr128Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,614,168 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

APOD
NM_001647.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.65

Variant links:

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]

APOD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013991833).

BP6

Variant 3-195569087-T-C is Benign according to our data. Variant chr3-195569087-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3038449.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOD	NM_001647.4 linkuse as main transcript	c.383A>G	p.Tyr128Cys	missense_variant	5/5	ENST00000343267.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
APOD	ENST00000343267.8 linkuse as main transcript	c.383A>G	p.Tyr128Cys	missense_variant	5/5	1	NM_001647.4	P1
APOD	ENST00000421243.5 linkuse as main transcript	c.467A>G	p.Tyr156Cys	missense_variant	6/6	3
APOD	ENST00000453131.1 linkuse as main transcript	c.383A>G	p.Tyr128Cys	missense_variant	6/6	3
APOD	ENST00000458447.5 linkuse as main transcript	c.*178A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

283

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000457

AC:

115

AN:

251482

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

240

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00633

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.00187

AC:

284

AN:

152274

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00655

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.00205

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000626

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

APOD-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 27, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Uncertain

-0.028

MutationAssessor

Pathogenic

3.7

H;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.033

D;.;.

Polyphen

1.0

D;.;.

Vest4

0.78

MVP

0.82

MPC

0.67

ClinPred

0.18

GERP RS

5.9

Varity_R

0.84

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over