rs1390441413

Variant names:

• chr6-138404515-C-G
• NM_014320.3:c.20C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-138404515-C-G
• chr6-138404515-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014320.3(HEBP2):​c.20C>G​(p.Pro7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000086 in 1,163,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: HEBP2 NM_014320.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

HEBP2 (HGNC:15716): (heme binding protein 2) The protein encoded by this gene is found predominately in the cytoplasm, where it plays a role in the collapse of mitochondrial membrane potential (MMP) prior to necrotic cell death. The encoded protein enhances outer and inner mitochondrial membrane permeabilization, especially under conditions of oxidative stress. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14706299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEBP2	NM_014320.3	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 4	ENST00000607197.6	NP_055135.1
HEBP2	NM_001326381.2	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 4		NP_001313310.1
HEBP2	NM_001326380.2	c.136-630C>G		intron_variant	Intron 1 of 3		NP_001313309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEBP2	ENST00000607197.6	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 4	1	NM_014320.3	ENSP00000475750.1
HEBP2	ENST00000367697.7	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 4	2		ENSP00000356670.3
HEBP2	ENST00000448741.5	c.136-630C>G		intron_variant	Intron 1 of 3	5		ENSP00000392101.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.60e-7 AC: 1 AN: 1163384 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 563222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000371

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.88	.;N
REVEL	Benign	0.051
Sift	Uncertain	0.0050	.;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.92	P;.
Vest4		0.47
MutPred		0.26		Gain of solvent accessibility (P = 0.0216);Gain of solvent accessibility (P = 0.0216);
MVP		0.41
MPC		0.15
ClinPred		0.48	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.066
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-138725652;