2-241273257-A-G

Variant names:

• chr2-241273257-A-G
• rs6705421
• NM_005336.6:c.-102-4716T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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:56103): (HDLBP antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.-102-4716T>C		intron_variant	Intron 1 of 27	ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.-102-4716T>C		intron_variant	Intron 1 of 27	1	NM_005336.6	ENSP00000312042.4

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

African (AFR) AF: 0.380 AC: 5989 AN: 15766

American (AMR) AF: 0.689 AC: 678 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 2810 AN: 5152

East Asian (EAS) AF: 0.784 AC: 2843 AN: 3628

South Asian (SAS) AF: 0.619 AC: 10174 AN: 16440

European-Finnish (FIN) AF: 0.643 AC: 180 AN: 280

Middle Eastern (MID) AF: 0.546 AC: 885 AN: 1620

European-Non Finnish (NFE) AF: 0.559 AC: 425801 AN: 761158

Other (OTH) AF: 0.567 AC: 15476 AN: 27292

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

African (AFR) AF: 0.397 AC: 16465 AN: 41458

American (AMR) AF: 0.646 AC: 9878 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3470

East Asian (EAS) AF: 0.778 AC: 4016 AN: 5162

South Asian (SAS) AF: 0.620 AC: 2990 AN: 4824

European-Finnish (FIN) AF: 0.525 AC: 5537 AN: 10544

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.546 AC: 37074 AN: 67932

Other (OTH) AF: 0.560 AC: 1181 AN: 2108

Alfa AF: 0.540 Hom.: 62118

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
PhyloP100		-1.6
PromoterAI		-0.025	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6705421; hg19: chr2-242212672;