rs4675971

Variant names:

• chr2-241257758-G-A
• rs4675971
• NM_005336.6:c.451-952C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-241257758-G-A
• chr2-241257758-G-C
• chr2-241257758-G-T

Variant summary

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

The NM_005336.6(HDLBP):​c.451-952C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,054 control chromosomes in the GnomAD database, including 3,822 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 0.21 (3822 hom., cov: 32)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005336.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	NM_005336.6	MANE Select	c.451-952C>T		intron	N/A	NP_005327.1	A0A024R4E5
	HDLBP	NM_001320965.3		c.451-952C>T		intron	N/A	NP_001307894.1	Q00341-1
	HDLBP	NM_001320966.3		c.451-952C>T		intron	N/A	NP_001307895.1	Q00341-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.451-952C>T		intron	N/A	ENSP00000312042.4	Q00341-1
	HDLBP	ENST00000391975.5	TSL:1	c.451-952C>T		intron	N/A	ENSP00000375836.1	Q00341-1
	HDLBP	ENST00000875612.1		c.451-952C>T		intron	N/A	ENSP00000545671.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31421 AN: 151936 Hom.: 3795 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.207 AC: 31497 AN: 152054 Hom.: 3822 Cov.: 32 AF XY: 0.209 AC XY: 15573 AN XY: 74342

African (AFR) AF: 0.212 AC: 8783 AN: 41482

American (AMR) AF: 0.364 AC: 5556 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2049 AN: 5164

South Asian (SAS) AF: 0.243 AC: 1168 AN: 4812

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10584

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11214 AN: 67954

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.191 Hom.: 5370

Bravo AF: 0.230

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.32
PhyloP100		-0.022
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: rs4675971; hg19: chr2-242197173;