2-241229561-T-C

Variant names:

• chr2-241229561-T-C
• rs15129
• NM_005336.6:c.*40A>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.*40A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,471,092 control chromosomes in the GnomAD database, including 49,240 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 0.24 (5488 hom., cov: 32)
  • Exomes 𝑓: 0.23 (43752 hom.)
• Consequence: HDLBP NM_005336.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• Publications: 20 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	NM_005336.6	MANE Select	c.*40A>G		3_prime_UTR	Exon 28 of 28	NP_005327.1
	HDLBP	NM_001320965.3		c.*40A>G		3_prime_UTR	Exon 28 of 28	NP_001307894.1
	HDLBP	NM_001320966.3		c.*40A>G		3_prime_UTR	Exon 28 of 28	NP_001307895.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.*40A>G		3_prime_UTR	Exon 28 of 28	ENSP00000312042.4
	HDLBP	ENST00000391975.5	TSL:1	c.*40A>G		3_prime_UTR	Exon 28 of 28	ENSP00000375836.1
	HDLBP	ENST00000484412.1	TSL:5	n.547A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36372 AN: 151928 Hom.: 5461 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.305 AC: 73346 AN: 240312 AF XY: 0.296

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.758

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.230 AC: 303044 AN: 1319046 Hom.: 43752 Cov.: 18 AF XY: 0.230 AC XY: 152741 AN XY: 663038

African (AFR) AF: 0.190 AC: 5804 AN: 30536

American (AMR) AF: 0.462 AC: 20053 AN: 43404

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4152 AN: 24856

East Asian (EAS) AF: 0.720 AC: 27969 AN: 38866

South Asian (SAS) AF: 0.337 AC: 27590 AN: 81896

European-Finnish (FIN) AF: 0.336 AC: 17780 AN: 52924

Middle Eastern (MID) AF: 0.154 AC: 760 AN: 4920

European-Non Finnish (NFE) AF: 0.189 AC: 185909 AN: 986160

Other (OTH) AF: 0.235 AC: 13027 AN: 55484

GnomAD4 genome AF: 0.240 AC: 36439 AN: 152046 Hom.: 5488 Cov.: 32 AF XY: 0.252 AC XY: 18717 AN XY: 74322

African (AFR) AF: 0.196 AC: 8144 AN: 41484

American (AMR) AF: 0.324 AC: 4956 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 589 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3833 AN: 5148

South Asian (SAS) AF: 0.354 AC: 1706 AN: 4818

European-Finnish (FIN) AF: 0.350 AC: 3708 AN: 10580

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12858 AN: 67960

Other (OTH) AF: 0.237 AC: 499 AN: 2106

Alfa AF: 0.210 Hom.: 11371

Bravo AF: 0.241

Asia WGS AF: 0.528 AC: 1833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.46
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs15129; hg19: chr2-242168976; COSMIC: COSV51471860; COSMIC: COSV51471860;