2-241235916-T-C

Variant names:

• chr2-241235916-T-C
• rs6437249
• NM_005336.6:c.2905-322A>G

Variant summary

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

The NM_005336.6(HDLBP):​c.2905-322A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 151,774 control chromosomes in the GnomAD database, including 38,991 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 0.71 (38991 hom., cov: 31)
• Consequence: HDLBP NM_005336.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.863
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDLBP	NM_005336.6	c.2905-322A>G		intron_variant	Intron 21 of 27	ENST00000310931.10	NP_005327.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDLBP	ENST00000310931.10	c.2905-322A>G		intron_variant	Intron 21 of 27	1	NM_005336.6	ENSP00000312042.4

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108330 AN: 151656 Hom.: 38943 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.714 AC: 108437 AN: 151774 Hom.: 38991 Cov.: 31 AF XY: 0.720 AC XY: 53392 AN XY: 74186

African (AFR) AF: 0.694 AC: 28730 AN: 41396

American (AMR) AF: 0.770 AC: 11752 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2608 AN: 3464

East Asian (EAS) AF: 0.935 AC: 4807 AN: 5140

South Asian (SAS) AF: 0.614 AC: 2956 AN: 4814

European-Finnish (FIN) AF: 0.744 AC: 7816 AN: 10512

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47255 AN: 67878

Other (OTH) AF: 0.747 AC: 1573 AN: 2106

Alfa AF: 0.712 Hom.: 46657

Bravo AF: 0.724

Asia WGS AF: 0.794 AC: 2763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.26
PhyloP100		-0.86
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: rs6437249; hg19: chr2-242175331;