rs1057058

Positions:

• chr15-59672705-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_004330.4(BNIP2):​c.507G>A​(p.Val169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,612,956 control chromosomes in the GnomAD database, including 865 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 0.021 (58 hom., cov: 33)
  • Exomes 𝑓: 0.030 (807 hom.)
• Consequence: BNIP2 NM_004330.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490

Genes affected

BNIP2 (HGNC:1083): (BCL2 interacting protein 2) This gene is a member of the BCL2/adenovirus E1B 19 kd-interacting protein (BNIP) family. It interacts with the E1B 19 kDa protein, which protects cells from virally-induced cell death. The encoded protein also interacts with E1B 19 kDa-like sequences of BCL2, another apoptotic protector. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.49 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0212 (3222/152200) while in subpopulation NFE AF= 0.0335 (2278/67996). AF 95% confidence interval is 0.0324. There are 58 homozygotes in gnomad4. There are 1496 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BNIP2	NM_004330.4	c.507G>A	p.Val169=	synonymous_variant	6/10	ENST00000607373.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BNIP2	ENST00000607373.6	c.507G>A	p.Val169=	synonymous_variant	6/10	1	NM_004330.4	P3

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3224 AN: 152082 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.00710

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.0215 AC: 5389 AN: 250976 Hom.: 96 AF XY: 0.0214 AC XY: 2898 AN XY: 135642

Gnomad AFR exome AF: 0.00695

Gnomad AMR exome AF: 0.0125

Gnomad ASJ exome AF: 0.0346

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00268

Gnomad FIN exome AF: 0.0135

Gnomad NFE exome AF: 0.0351

Gnomad OTH exome AF: 0.0227

GnomAD4 exome AF: 0.0304 AC: 44342 AN: 1460756 Hom.: 807 Cov.: 31 AF XY: 0.0297 AC XY: 21585 AN XY: 726672

Gnomad4 AFR exome AF: 0.00634

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.0340

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00339

Gnomad4 FIN exome AF: 0.0146

Gnomad4 NFE exome AF: 0.0358

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.0212 AC: 3222 AN: 152200 Hom.: 58 Cov.: 33 AF XY: 0.0201 AC XY: 1496 AN XY: 74408

Gnomad4 AFR AF: 0.00706

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0309 Hom.: 54

Bravo AF: 0.0217

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0318

EpiControl AF: 0.0328

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	6.2
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1057058; hg19: chr15-59964904;