2-241246976-C-T

Position:

• chr2-241246976-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.1818+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 1,574,166 control chromosomes in the GnomAD database, including 7,668 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 0.11 (899 hom., cov: 32)
  • Exomes 𝑓: 0.095 (6769 hom.)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.1818+80G>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.1818+80G>A		intron_variant		1	NM_005336.6	ENSP00000312042	P1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16162 AN: 152126 Hom.: 897 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0954 AC: 135640 AN: 1421922 Hom.: 6769 Cov.: 24 AF XY: 0.0964 AC XY: 68438 AN XY: 709790

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0498

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0832

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0767

Gnomad4 NFE exome AF: 0.0939

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.106 AC: 16172 AN: 152244 Hom.: 899 Cov.: 32 AF XY: 0.106 AC XY: 7870 AN XY: 74440

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0744

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.0726

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0704

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.111

Alfa AF: 0.102 Hom.: 443

Bravo AF: 0.108

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.68
DANN	Benign	0.46

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: rs2305076; hg19: chr2-242186391;