Variant rs7578199 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005336.6(HDLBP):c.1253A>G(p.Asn418Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,610,946 control chromosomes in the GnomAD database, including 40,645 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 3605 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37040 hom. )

Consequence

HDLBP
NM_005336.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0160

Variant links:

Genes affected

HDLBP (HGNC:4857): (high density lipoprotein binding protein) The protein encoded by this gene binds high density lipoprotein (HDL) and may function to regulate excess cholesterol levels in cells. The encoded protein also binds RNA and can induce heterochromatin formation. [provided by RefSeq, Mar 2016]

HDLBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039993525).

BP6

Variant 2-241253433-T-C is Benign according to our data. Variant chr2-241253433-T-C is described in ClinVar as [Benign]. Clinvar id is 3060902.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDLBP	NM_005336.6 linkuse as main transcript	c.1253A>G	p.Asn418Ser	missense_variant	10/28	ENST00000310931.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDLBP	ENST00000310931.10 linkuse as main transcript	c.1253A>G	p.Asn418Ser	missense_variant	10/28	1	NM_005336.6	P1

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31715

AN:

152030

Hom.:

3605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0695

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.227

GnomAD3 exomes

AF:

0.186

AC:

46672

AN:

251434

Hom.:

5386

AF XY:

0.186

AC XY:

25330

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.0711

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.248

Gnomad OTH exome

AF:

0.230

GnomAD4 exome

AF:

0.215

AC:

314337

AN:

1458798

Hom.:

37040

Cov.:

AF XY:

0.213

AC XY:

154864

AN XY:

725912

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.296

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.0719

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.208

AC:

31713

AN:

152148

Hom.:

3605

Cov.:

AF XY:

0.206

AC XY:

15317

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.303

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0687

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.237

Hom.:

11407

Bravo

AF:

0.210

TwinsUK

AF:

0.231

AC:

856

ALSPAC

AF:

0.238

AC:

918

ESP6500AA

AF:

0.183

AC:

805

ESP6500EA

AF:

0.246

AC:

2118

ExAC

AF:

0.187

AC:

22657

EpiCase

AF:

0.270

EpiControl

AF:

0.271

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HDLBP-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as 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

Benign

0.056

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0060

DANN

Benign

0.38

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.76

.;.;.;T

MetaRNN

Benign

0.0040

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.56

N;N;N;N

REVEL

Benign

0.068

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.26

T;T;T;T

Vest4

0.022

MPC

0.55

ClinPred

0.017

GERP RS

-12

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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