Variant 2-241236773-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005336.6(HDLBP):c.2750-4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,612,712 control chromosomes in the GnomAD database, including 10,299 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.082 ( 655 hom., cov: 31)

Exomes 𝑓: 0.11 ( 9644 hom. )

Consequence

HDLBP
NM_005336.6 splice_region, intron

Scores

Splicing: ADA: 0.0001187

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.13

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:

HDLBP (HGNC:):

HDLBP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-241236773-G-C is Benign according to our data. Variant chr2-241236773-G-C is described in ClinVar as [Benign]. Clinvar id is 3055900.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDLBP	NM_005336.6 linkuse as main transcript	c.2750-4C>G		splice_region_variant, intron_variant		ENST00000310931.10	NP_005327.1	Q00341A0A024R4E5B2R5V9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10 linkuse as main transcript	c.2750-4C>G		splice_region_variant, intron_variant		1	NM_005336.6	ENSP00000312042.4		A0A024R4E5

Frequencies

GnomAD3 genomes

AF:

0.0821

AC:

12483

AN:

152108

Hom.:

655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0599

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.0670

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0926

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.0967

GnomAD3 exomes

AF:

0.0977

AC:

24450

AN:

250336

Hom.:

1403

AF XY:

0.103

AC XY:

13936

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.0204

Gnomad AMR exome

AF:

0.0434

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.0629

Gnomad SAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.0968

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.111

AC:

162657

AN:

1460486

Hom.:

9644

Cov.:

AF XY:

0.113

AC XY:

81798

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.0177

Gnomad4 AMR exome

AF:

0.0452

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.0733

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.0820

AC:

12477

AN:

152226

Hom.:

655

Cov.:

AF XY:

0.0821

AC XY:

6106

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.0596

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.0667

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0926

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.0990

Alfa

AF:

0.112

Hom.:

333

Bravo

AF:

0.0772

Asia WGS

AF:

0.110

AC:

383

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HDLBP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 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

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.0020

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

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