NM_005336.6:c.3145-538C>T

Variant names:

• chr2-241234501-G-A
• rs3755325
• NM_005336.6:c.3145-538C>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.3145-538C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,000 control chromosomes in the GnomAD database, including 14,606 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 0.42 (14606 hom., cov: 32)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• 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]

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

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 = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.3145-538C>T		intron_variant	Intron 23 of 27	ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.3145-538C>T		intron_variant	Intron 23 of 27	1	NM_005336.6	ENSP00000312042.4

Frequencies

GnomAD3 genomes AF: 0.421 AC: 64008 AN: 151882 Hom.: 14603 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.465

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

GnomAD4 genome AF: 0.421 AC: 64029 AN: 152000 Hom.: 14606 Cov.: 32 AF XY: 0.415 AC XY: 30837 AN XY: 74304

African (AFR) AF: 0.287 AC: 11915 AN: 41458

American (AMR) AF: 0.457 AC: 6973 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3470

East Asian (EAS) AF: 0.159 AC: 818 AN: 5158

South Asian (SAS) AF: 0.250 AC: 1208 AN: 4824

European-Finnish (FIN) AF: 0.410 AC: 4330 AN: 10566

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35134 AN: 67942

Other (OTH) AF: 0.460 AC: 973 AN: 2114

Alfa AF: 0.489 Hom.: 26193

Bravo AF: 0.420

Asia WGS AF: 0.198 AC: 690 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	1.6
DANN	Benign	0.53
PhyloP100		-0.20
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: rs3755325; hg19: chr2-242173916;