Genetic Variant HDLBP:c.2904+9C>T (chr2-241236606-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005336.6(HDLBP):c.2904+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,613,674 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

HDLBP
NM_005336.6 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.47

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-241236606-G-A is Benign according to our data. Variant chr2-241236606-G-A is described in ClinVar as Benign. ClinVar VariationId is 3035706.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 461 AD gene.

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.2904+9C>T	intron	N/A	NP_005327.1	A0A024R4E5
HDLBP	NM_001320965.3		c.2904+9C>T	intron	N/A	NP_001307894.1	Q00341-1
HDLBP	NM_001320966.3		c.2904+9C>T	intron	N/A	NP_001307895.1	Q00341-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.2904+9C>T		intron	N/A	ENSP00000312042.4	Q00341-1
HDLBP	ENST00000391975.5	TSL:1	c.2904+9C>T		intron	N/A	ENSP00000375836.1	Q00341-1
HDLBP	ENST00000875612.1		c.2913C>T	p.Val971Val	synonymous	Exon 21 of 28	ENSP00000545671.1

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

459

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000706

AC:

177

AN:

250758

AF XY:

0.000458

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000314

AC:

459

AN:

1461448

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

192

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.0125

AC:

417

AN:

33478

American (AMR)

AF:

0.000201

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111716

Other (OTH)

AF:

0.000464

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00303

AC:

461

AN:

152226

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

196

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0107

AC:

445

AN:

41532

American (AMR)

AF:

0.000719

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68014

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00339

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

HDLBP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.7

(source)

DANN

Benign

0.46

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism

(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