chr2-241300503-G-A

Variant names:

• chr2-241300503-G-A
• rs7559564
• NM_005336.6:c.-103+15067C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	NM_005336.6	MANE Select	c.-103+15067C>T		intron	N/A	NP_005327.1
	HDLBP	NM_001320965.3		c.-103+14599C>T		intron	N/A	NP_001307894.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.-103+15067C>T		intron	N/A	ENSP00000312042.4
	HDLBP	ENST00000391976.6	TSL:5	c.-103+14599C>T		intron	N/A	ENSP00000375837.2
	HDLBP	ENST00000428482.5	TSL:5	c.-328+15067C>T		intron	N/A	ENSP00000405109.1

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

African (AFR) AF: 0.107 AC: 4423 AN: 41530

American (AMR) AF: 0.155 AC: 2366 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3468

East Asian (EAS) AF: 0.108 AC: 561 AN: 5172

South Asian (SAS) AF: 0.190 AC: 914 AN: 4822

European-Finnish (FIN) AF: 0.128 AC: 1352 AN: 10560

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13064 AN: 67994

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.185 Hom.: 4561

Bravo AF: 0.156

Asia WGS AF: 0.163 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.18
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7559564; hg19: chr2-242239918;