2-241250694-C-G

Position:

• chr2-241250694-C-G

Variant summary

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

The NM_005336.6(HDLBP):​c.1373-714G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,246 control chromosomes in the GnomAD database, including 3,513 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 0.20 (3512 hom., cov: 33)
  • Exomes 𝑓: 0.19 (1 hom.)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDLBP	NM_005336.6	c.1373-714G>C		intron_variant		ENST00000310931.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDLBP	ENST00000310931.10	c.1373-714G>C		intron_variant		1	NM_005336.6	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29854 AN: 152040 Hom.: 3510 Cov.: 33

Gnomad AFR AF: 0.0825

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.193 AC: 17 AN: 88 Hom.: 1 Cov.: 0 AF XY: 0.191 AC XY: 13 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.196 AC: 29859 AN: 152158 Hom.: 3512 Cov.: 33 AF XY: 0.192 AC XY: 14264 AN XY: 74374

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.219

Alfa AF: 0.118 Hom.: 221

Bravo AF: 0.192

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.58
DANN	Benign	0.76

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: rs3771346; hg19: chr2-242190109;