rs1057058

Variant names:

• chr15-59672705-C-T
• rs1057058
• NM_004330.4:c.507G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_001320674.2(BNIP2):​c.507G>A​(p.Val169Val) 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_001320674.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320674.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP2	NM_004330.4	MANE Select	c.507G>A	p.Val169Val	synonymous	Exon 6 of 10	NP_004321.3
	BNIP2	NM_001320674.2		c.507G>A	p.Val169Val	synonymous	Exon 6 of 11	NP_001307603.2
	BNIP2	NM_001320675.4		c.507G>A	p.Val169Val	synonymous	Exon 6 of 10	NP_001307604.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP2	ENST00000607373.6	TSL:1 MANE Select	c.507G>A	p.Val169Val	synonymous	Exon 6 of 10	ENSP00000475320.1
	BNIP2	ENST00000439052.6	TSL:2	c.507G>A	p.Val169Val	synonymous	Exon 6 of 11	ENSP00000393644.2
	BNIP2	ENST00000897502.1		c.507G>A	p.Val169Val	synonymous	Exon 6 of 11	ENSP00000567561.1

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

GnomAD2 exomes AF: 0.0215 AC: 5389 AN: 250976 AF XY: 0.0214

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 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

African (AFR) AF: 0.00634 AC: 212 AN: 33462

American (AMR) AF: 0.0132 AC: 590 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 889 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00339 AC: 292 AN: 86240

European-Finnish (FIN) AF: 0.0146 AC: 782 AN: 53392

Middle Eastern (MID) AF: 0.00971 AC: 56 AN: 5766

European-Non Finnish (NFE) AF: 0.0358 AC: 39782 AN: 1111100

Other (OTH) AF: 0.0288 AC: 1739 AN: 60330

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

African (AFR) AF: 0.00706 AC: 293 AN: 41520

American (AMR) AF: 0.0220 AC: 336 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 113 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.0120 AC: 127 AN: 10592

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0335 AC: 2278 AN: 67996

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0309 Hom.: 74

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	6.2
DANN	Benign	0.68
PhyloP100		0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=83/17	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: rs1057058; hg19: chr15-59964904;