2-241312124-G-T

Variant names:

• chr2-241312124-G-T
• rs1106523
• NM_005336.6:c.-103+3446C>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.-103+3446C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,106 control chromosomes in the GnomAD database, including 8,392 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 0.32 (8392 hom., cov: 33)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.-103+3446C>A		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.-103+3446C>A		intron_variant	Intron 1 of 27	1	NM_005336.6	ENSP00000312042.4

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48252 AN: 151986 Hom.: 8382 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.317 AC: 48280 AN: 152106 Hom.: 8392 Cov.: 33 AF XY: 0.321 AC XY: 23858 AN XY: 74340

African (AFR) AF: 0.177 AC: 7347 AN: 41502

American (AMR) AF: 0.274 AC: 4195 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3470

East Asian (EAS) AF: 0.513 AC: 2656 AN: 5178

South Asian (SAS) AF: 0.436 AC: 2101 AN: 4820

European-Finnish (FIN) AF: 0.387 AC: 4089 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25564 AN: 67966

Other (OTH) AF: 0.317 AC: 670 AN: 2112

Alfa AF: 0.315 Hom.: 6432

Bravo AF: 0.300

Asia WGS AF: 0.461 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.47
PhyloP100		0.32
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: rs1106523; hg19: chr2-242251539;