rs4766807

Variant names:

• chr12-116863646-T-A
• rs4766807
• NM_003806.4:c.*57-2180A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-116863646-T-A
• chr12-116863646-T-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.*57-2180A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,910 control chromosomes in the GnomAD database, including 22,949 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 0.50 (22949 hom., cov: 30)
• Consequence: HRK NM_003806.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.649 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.*57-2180A>T		intron	N/A	NP_003797.1	O00198
	HRK	NR_073189.3		n.807-2180A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HRK	ENST00000257572.5	TSL:1 MANE Select	c.*57-2180A>T		intron	N/A	ENSP00000257572.4	O00198
	HRK	ENST00000550505.5	TSL:5	c.*397-2180A>T		intron	N/A	ENSP00000465379.1	K7EJY7
	HRK	ENST00000552092.1	TSL:3	n.546-2180A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75369 AN: 151800 Hom.: 22936 Cov.: 30

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.496 AC: 75388 AN: 151910 Hom.: 22949 Cov.: 30 AF XY: 0.500 AC XY: 37158 AN XY: 74260

African (AFR) AF: 0.127 AC: 5240 AN: 41420

American (AMR) AF: 0.659 AC: 10068 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2000 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2434 AN: 5168

South Asian (SAS) AF: 0.477 AC: 2299 AN: 4820

European-Finnish (FIN) AF: 0.694 AC: 7317 AN: 10538

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.652 AC: 44270 AN: 67914

Other (OTH) AF: 0.518 AC: 1094 AN: 2110

Alfa AF: 0.445 Hom.: 1603

Bravo AF: 0.479

Asia WGS AF: 0.461 AC: 1604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.079
DANN	Benign	0.53
PhyloP100		-1.9
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: rs4766807; hg19: chr12-117301451;