rs4766807

Positions:

• chr12-116863646-T-A
• chr12-116863646-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HRK	NM_003806.4	c.*57-2180A>T		intron_variant		ENST00000257572.5	NP_003797.1
HRK	NR_073189.3	n.807-2180A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HRK	ENST00000257572.5	c.*57-2180A>T		intron_variant		1	NM_003806.4	ENSP00000257572	P1
HRK	ENST00000550505.5	c.*397-2180A>T		intron_variant		5		ENSP00000465379
HRK	ENST00000552092.1	n.546-2180A>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.518

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.079
DANN	Benign	0.53

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: rs4766807; hg19: chr12-117301451;