Genetic Variant HDLBP:p.Asn418Ser (chr2-241253433-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: 0.0160

Publications

42 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 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 VariationId is 3060902.Status of the report is no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
HDLBP	NM_005336.6 link	c.1253A>G	p.Asn418Ser	missense_variant	Exon 10 of 28	ENST00000310931.10	NP_005327.1	Q00341A0A024R4E5B2R5V9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10 link	c.1253A>G	p.Asn418Ser	missense_variant	Exon 10 of 28	1	NM_005336.6	ENSP00000312042.4		A0A024R4E5

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

GnomAD2 exomes

AF:

0.186

AC:

46672

AN:

251434

AF XY:

0.186

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 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

African (AFR)

AF:

0.180

AC:

6030

AN:

33430

American (AMR)

AF:

0.138

AC:

6178

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.296

AC:

7740

AN:

26114

East Asian (EAS)

AF:

0.000554

AC:

AN:

39700

South Asian (SAS)

AF:

0.0719

AC:

6204

AN:

86242

European-Finnish (FIN)

AF:

0.207

AC:

11038

AN:

53410

Middle Eastern (MID)

AF:

0.275

AC:

1586

AN:

5758

European-Non Finnish (NFE)

AF:

0.237

AC:

262789

AN:

1109152

Other (OTH)

AF:

0.212

AC:

12750

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

11120

22239

33359

44478

55598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8544

17088

25632

34176

42720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.208

AC:

31713

AN:

152148

Hom.:

3605

Cov.:

AF XY:

0.206

AC XY:

15317

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.176

AC:

7287

AN:

41492

American (AMR)

AF:

0.189

AC:

2884

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1051

AN:

3464

East Asian (EAS)

AF:

0.00212

AC:

AN:

5178

South Asian (SAS)

AF:

0.0687

AC:

332

AN:

4830

European-Finnish (FIN)

AF:

0.216

AC:

2285

AN:

10588

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16797

AN:

67982

Other (OTH)

AF:

0.224

AC:

474

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1257

2514

3771

5028

6285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.234

Hom.:

14391

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: no assertion criteria provided

LINK: link

Submissions by phenotype

HDLBP-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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

PhyloP100

0.016

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over