Genetic Variant NM_005336.6:c.2749+499T>G (chr2-241238150-A-C) – 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.2749+499T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,428 control chromosomes in the GnomAD database, including 6,153 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 0.27 ( 6141 hom., cov: 33)

Exomes 𝑓: 0.30 ( 12 hom. )

Consequence

HDLBP
NM_005336.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.693

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:

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

ANO7 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDLBP	NM_005336.6 link	c.2749+499T>G		intron_variant	Intron 20 of 27	ENST00000310931.10	NP_005327.1	Q00341A0A024R4E5B2R5V9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10 link	c.2749+499T>G		intron_variant	Intron 20 of 27	1	NM_005336.6	ENSP00000312042.4		A0A024R4E5

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40638

AN:

152094

Hom.:

6140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.373

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.301

AC:

AN:

216

Hom.:

AF XY:

0.295

AC XY:

AN XY:

112

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.289

AC:

AN:

166

Other (OTH)

AF:

0.375

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.267

AC:

40667

AN:

152212

Hom.:

6141

Cov.:

AF XY:

0.276

AC XY:

20543

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.184

AC:

7641

AN:

41548

American (AMR)

AF:

0.192

AC:

2941

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

956

AN:

3468

East Asian (EAS)

AF:

0.635

AC:

3279

AN:

5162

South Asian (SAS)

AF:

0.374

AC:

1803

AN:

4824

European-Finnish (FIN)

AF:

0.399

AC:

4226

AN:

10598

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.280

AC:

19018

AN:

67998

Other (OTH)

AF:

0.262

AC:

553

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1513

3026

4539

6052

7565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.270

Hom.:

15411

Bravo

AF:

0.249

Asia WGS

AF:

0.464

AC:

1615

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.25

(source)

DANN

Benign

0.51

PhyloP100

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over