Genetic Variant HDLBP:c.1373-714G>C (chr2-241250694-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005336.6(HDLBP):c.1373-714G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,246 control chromosomes in the GnomAD database, including 3,513 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 0.20 ( 3512 hom., cov: 33)

Exomes 𝑓: 0.19 ( 1 hom. )

Consequence

HDLBP
NM_005336.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005336.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HDLBP	NM_005336.6	MANE Select	c.1373-714G>C	intron	N/A	NP_005327.1	A0A024R4E5
HDLBP	NM_001320965.3		c.1373-714G>C	intron	N/A	NP_001307894.1	Q00341-1
HDLBP	NM_001320966.3		c.1373-714G>C	intron	N/A	NP_001307895.1	Q00341-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.1373-714G>C	intron	N/A	ENSP00000312042.4	Q00341-1
HDLBP	ENST00000391975.5	TSL:1	c.1373-714G>C	intron	N/A	ENSP00000375836.1	Q00341-1
HDLBP	ENST00000875612.1		c.1373-714G>C	intron	N/A	ENSP00000545671.1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29854

AN:

152040

Hom.:

3510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.259

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.221

GnomAD4 exome

AF:

0.193

AC:

AN:

Hom.:

Cov.:

AF XY:

0.191

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.214

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.203

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.196

AC:

29859

AN:

152158

Hom.:

3512

Cov.:

AF XY:

0.192

AC XY:

14264

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0826

AC:

3430

AN:

41528

American (AMR)

AF:

0.250

AC:

3820

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

899

AN:

3472

East Asian (EAS)

AF:

0.155

AC:

801

AN:

5154

South Asian (SAS)

AF:

0.175

AC:

842

AN:

4822

European-Finnish (FIN)

AF:

0.191

AC:

2022

AN:

10576

Middle Eastern (MID)

AF:

0.271

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.256

AC:

17403

AN:

67994

Other (OTH)

AF:

0.219

AC:

464

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1213

2426

3639

4852

6065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.118

Hom.:

221

Bravo

AF:

0.192

Asia WGS

AF:

0.150

AC:

521

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.58

(source)

DANN

Benign

0.76

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over