2-241257680-C-T

Position:

• chr2-241257680-C-T

Variant summary

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

The NM_005336.6(HDLBP):​c.451-874G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,076 control chromosomes in the GnomAD database, including 9,233 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 0.34 (9233 hom., cov: 33)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.451-874G>A		intron_variant		ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.451-874G>A		intron_variant		1	NM_005336.6	ENSP00000312042	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50918 AN: 151960 Hom.: 9195 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.335 AC: 51010 AN: 152076 Hom.: 9233 Cov.: 33 AF XY: 0.343 AC XY: 25477 AN XY: 74332

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.328

Alfa AF: 0.301 Hom.: 9403

Bravo AF: 0.346

Asia WGS AF: 0.591 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.48

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: rs4675973; hg19: chr2-242197095;