NM_005336.6:c.1732-280G>A

Variant names:

• chr2-241247422-C-T
• rs11680329
• NM_005336.6:c.1732-280G>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.1732-280G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 458,524 control chromosomes in the GnomAD database, including 6,740 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 0.14 (1962 hom., cov: 32)
  • Exomes 𝑓: 0.16 (4778 hom.)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.1732-280G>A		intron_variant	Intron 14 of 27	ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.1732-280G>A		intron_variant	Intron 14 of 27	1	NM_005336.6	ENSP00000312042.4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21338 AN: 152110 Hom.: 1963 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0520

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.159 AC: 48690 AN: 306296 Hom.: 4778 Cov.: 0 AF XY: 0.153 AC XY: 25003 AN XY: 163748

African (AFR) AF: 0.0388 AC: 358 AN: 9222

American (AMR) AF: 0.118 AC: 1681 AN: 14212

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 1815 AN: 8860

East Asian (EAS) AF: 0.000276 AC: 5 AN: 18140

South Asian (SAS) AF: 0.0573 AC: 2336 AN: 40792

European-Finnish (FIN) AF: 0.164 AC: 2626 AN: 16002

Middle Eastern (MID) AF: 0.162 AC: 202 AN: 1250

European-Non Finnish (NFE) AF: 0.204 AC: 36965 AN: 180840

Other (OTH) AF: 0.159 AC: 2702 AN: 16978

GnomAD4 genome AF: 0.140 AC: 21325 AN: 152228 Hom.: 1962 Cov.: 32 AF XY: 0.139 AC XY: 10342 AN XY: 74440

African (AFR) AF: 0.0396 AC: 1646 AN: 41552

American (AMR) AF: 0.134 AC: 2054 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0512 AC: 247 AN: 4824

European-Finnish (FIN) AF: 0.185 AC: 1957 AN: 10598

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13925 AN: 67986

Other (OTH) AF: 0.155 AC: 328 AN: 2116

Alfa AF: 0.175 Hom.: 1015

Bravo AF: 0.135

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.36
DANN	Benign	0.51
PhyloP100		-1.5
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: rs11680329; hg19: chr2-242186837;