rs17429217

Positions:

• chr12-116857528-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003806.4(HRK):​c.*3995T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,328 control chromosomes in the GnomAD database, including 58 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 0.020 (58 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: HRK NM_003806.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.817

Genes affected

HRK (HGNC:5185): (harakiri, BCL2 interacting protein) This gene encodes a member of the BCL-2 protein family. Members of this family are involved in activating or inhibiting apoptosis. The encoded protein localizes to intracellular membranes. This protein promotes apoptosis by interacting with the apoptotic inhibitors BCL-2 and BCL-X(L) via its BH3 domain. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HRK	NM_003806.4	c.*3995T>C		3_prime_UTR_variant	2/2	ENST00000257572.5
HRK	NR_073189.3	n.4745T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HRK	ENST00000257572.5	c.*3995T>C		3_prime_UTR_variant	2/2	1	NM_003806.4	P1

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2986 AN: 152204 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0302

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0196 AC: 2981 AN: 152322 Hom.: 58 Cov.: 32 AF XY: 0.0194 AC XY: 1442 AN XY: 74488

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.0262

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0250 Hom.: 53

Bravo AF: 0.0195

Asia WGS AF: 0.0150 AC: 54 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	2.9
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs17429217; hg19: chr12-117295333;