2-241238150-A-C

Position:

• chr2-241238150-A-C

Variant summary

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

The NM_005336.6(HDLBP):​c.2749+499T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,428 control chromosomes in the GnomAD database, including 6,153 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 0.27 (6141 hom., cov: 33)
  • Exomes 𝑓: 0.30 (12 hom.)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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]

ANO7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDLBP	NM_005336.6	c.2749+499T>G		intron_variant		ENST00000310931.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDLBP	ENST00000310931.10	c.2749+499T>G		intron_variant		1	NM_005336.6	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40638 AN: 152094 Hom.: 6140 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.301 AC: 65 AN: 216 Hom.: 12 AF XY: 0.295 AC XY: 33 AN XY: 112

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.267 AC: 40667 AN: 152212 Hom.: 6141 Cov.: 33 AF XY: 0.276 AC XY: 20543 AN XY: 74428

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.635

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.262

Alfa AF: 0.275 Hom.: 9950

Bravo AF: 0.249

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.25
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2289795; hg19: chr2-242177565;