NM_003806.4:c.*3995T>C

Variant names:

• chr12-116857528-A-G
• rs17429217
• NM_003806.4:c.*3995T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003806.4. 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
	HRK	NM_003806.4	MANE Select	c.*3995T>C		3_prime_UTR	Exon 2 of 2	NP_003797.1	O00198
	HRK	NR_073189.3		n.4745T>C		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRK	ENST00000257572.5	TSL:1 MANE Select	c.*3995T>C		3_prime_UTR	Exon 2 of 2	ENSP00000257572.4	O00198

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0106 AC: 442 AN: 41586

American (AMR) AF: 0.0244 AC: 374 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0292 AC: 141 AN: 4830

European-Finnish (FIN) AF: 0.0104 AC: 110 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1782 AN: 68020

Other (OTH) AF: 0.0294 AC: 62 AN: 2110

Alfa AF: 0.0235 Hom.: 151

Bravo AF: 0.0195

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.68
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism

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: rs17429217; hg19: chr12-117295333;