rs4675971

Positions:

• chr2-241257758-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.451-952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,054 control chromosomes in the GnomAD database, including 3,822 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 0.21 (3822 hom., cov: 32)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.451-952C>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.451-952C>T		intron_variant		1	NM_005336.6	ENSP00000312042	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31421 AN: 151936 Hom.: 3795 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.207 AC: 31497 AN: 152054 Hom.: 3822 Cov.: 32 AF XY: 0.209 AC XY: 15573 AN XY: 74342

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.253

Alfa AF: 0.186 Hom.: 3982

Bravo AF: 0.230

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.32

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: rs4675971; hg19: chr2-242197173;