rs6705421

Positions:

• chr2-241273257-A-G
• chr2-241273257-A-T

Variant summary

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

The NM_005336.6(HDLBP):​c.-102-4716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 984,306 control chromosomes in the GnomAD database, including 151,852 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 0.52 (21600 hom., cov: 30)
  • Exomes 𝑓: 0.56 (130252 hom.)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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]

HDLBP-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDLBP	NM_005336.6	c.-102-4716T>C		intron_variant		ENST00000310931.10
HDLBP-AS1	NR_168372.1	n.1094A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDLBP	ENST00000310931.10	c.-102-4716T>C		intron_variant		1	NM_005336.6	P1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79340 AN: 151868 Hom.: 21553 Cov.: 30

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.558 AC: 464836 AN: 832320 Hom.: 130252 Cov.: 24 AF XY: 0.558 AC XY: 214308 AN XY: 384408

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.689

Gnomad4 ASJ exome AF: 0.545

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.643

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.523 AC: 79437 AN: 151986 Hom.: 21600 Cov.: 30 AF XY: 0.526 AC XY: 39066 AN XY: 74276

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.560

Alfa AF: 0.546 Hom.: 36490

Bravo AF: 0.525

Asia WGS AF: 0.733 AC: 2548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.49

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: rs6705421; hg19: chr2-242212672;