rs7559564

Positions:

• chr2-241300503-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005336.6(HDLBP):​c.-103+15067C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,136 control chromosomes in the GnomAD database, including 2,100 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 0.16 (2100 hom., cov: 32)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.-103+15067C>T		intron_variant		ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.-103+15067C>T		intron_variant		1	NM_005336.6	ENSP00000312042.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24074 AN: 152018 Hom.: 2096 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.173

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.158 AC: 24089 AN: 152136 Hom.: 2100 Cov.: 32 AF XY: 0.157 AC XY: 11686 AN XY: 74364

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.175

Alfa AF: 0.188 Hom.: 3650

Bravo AF: 0.156

Asia WGS AF: 0.163 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs7559564; hg19: chr2-242239918;