2-241257680-C-T

Variant names:

• chr2-241257680-C-T
• rs4675973
• NM_005336.6:c.451-874G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005336.6(HDLBP):​c.451-874G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,076 control chromosomes in the GnomAD database, including 9,233 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 0.34 (9233 hom., cov: 33)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.451-874G>A		intron_variant	Intron 5 of 27	ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.451-874G>A		intron_variant	Intron 5 of 27	1	NM_005336.6	ENSP00000312042.4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50918 AN: 151960 Hom.: 9195 Cov.: 33

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.335 AC: 51010 AN: 152076 Hom.: 9233 Cov.: 33 AF XY: 0.343 AC XY: 25477 AN XY: 74332

African (AFR) AF: 0.352 AC: 14609 AN: 41456

American (AMR) AF: 0.387 AC: 5907 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3763 AN: 5182

South Asian (SAS) AF: 0.452 AC: 2180 AN: 4818

European-Finnish (FIN) AF: 0.313 AC: 3310 AN: 10568

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19228 AN: 67986

Other (OTH) AF: 0.328 AC: 693 AN: 2114

Alfa AF: 0.309 Hom.: 13991

Bravo AF: 0.346

Asia WGS AF: 0.591 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.48
PhyloP100		-0.37
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: rs4675973; hg19: chr2-242197095;