rs6757876

Positions:

• chr2-241306155-T-C

Variant summary

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

The NM_005336.6(HDLBP):​c.-103+9415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,954 control chromosomes in the GnomAD database, including 2,590 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 0.17 (2590 hom., cov: 30)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

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 (AMR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.-103+9415A>G		intron_variant		ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.-103+9415A>G		intron_variant		1	NM_005336.6	ENSP00000312042	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25054 AN: 151834 Hom.: 2573 Cov.: 30

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.165 AC: 25093 AN: 151954 Hom.: 2590 Cov.: 30 AF XY: 0.167 AC XY: 12434 AN XY: 74256

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.216

Alfa AF: 0.169 Hom.: 3640

Bravo AF: 0.180

Asia WGS AF: 0.259 AC: 900 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	0.69
DANN	Benign	0.64

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: rs6757876; hg19: chr2-242245570;