chr2-241246976-C-T

Variant names:

• chr2-241246976-C-T
• rs2305076
• NM_005336.6:c.1818+80G>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.1818+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 1,574,166 control chromosomes in the GnomAD database, including 7,668 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 0.11 (899 hom., cov: 32)
  • Exomes 𝑓: 0.095 (6769 hom.)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.1818+80G>A		intron_variant	Intron 15 of 27	ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.1818+80G>A		intron_variant	Intron 15 of 27	1	NM_005336.6	ENSP00000312042.4

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16162 AN: 152126 Hom.: 897 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0704

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0954 AC: 135640 AN: 1421922 Hom.: 6769 Cov.: 24 AF XY: 0.0964 AC XY: 68438 AN XY: 709790

African (AFR) AF: 0.144 AC: 4678 AN: 32578

American (AMR) AF: 0.0498 AC: 2222 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3097 AN: 25876

East Asian (EAS) AF: 0.0832 AC: 3285 AN: 39478

South Asian (SAS) AF: 0.119 AC: 10190 AN: 85360

European-Finnish (FIN) AF: 0.0767 AC: 4094 AN: 53392

Middle Eastern (MID) AF: 0.162 AC: 922 AN: 5706

European-Non Finnish (NFE) AF: 0.0939 AC: 101054 AN: 1075918

Other (OTH) AF: 0.103 AC: 6098 AN: 58986

GnomAD4 genome AF: 0.106 AC: 16172 AN: 152244 Hom.: 899 Cov.: 32 AF XY: 0.106 AC XY: 7870 AN XY: 74440

African (AFR) AF: 0.145 AC: 6021 AN: 41534

American (AMR) AF: 0.0744 AC: 1138 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 449 AN: 3466

East Asian (EAS) AF: 0.0726 AC: 376 AN: 5182

South Asian (SAS) AF: 0.119 AC: 572 AN: 4824

European-Finnish (FIN) AF: 0.0704 AC: 746 AN: 10598

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6530 AN: 68022

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.102 Hom.: 489

Bravo AF: 0.108

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.68
DANN	Benign	0.46
PhyloP100		-1.7
PromoterAI		0.0074	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: rs2305076; hg19: chr2-242186391; COSMIC: COSV107314731; COSMIC: COSV107314731;