rs8543

Positions:

• chr5-173164334-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001205.3(BNIP1):​c.*413T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 161,344 control chromosomes in the GnomAD database, including 847 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 0.088 (774 hom., cov: 32)
  • Exomes 𝑓: 0.12 (73 hom.)
• Consequence: BNIP1 NM_001205.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

Genes affected

BNIP1 (HGNC:1082): (BCL2 interacting protein 1) 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. In addition, this protein is involved in vesicle transport into the endoplasmic reticulum. Alternative splicing of this gene results in four protein products with identical N- and C-termini. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BNIP1	NM_001205.3	c.*413T>G		3_prime_UTR_variant	6/6	ENST00000351486.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BNIP1	ENST00000351486.10	c.*413T>G		3_prime_UTR_variant	6/6	1	NM_001205.3	P1
BNIP1	ENST00000231668.13	c.*413T>G		3_prime_UTR_variant	7/7	1
BNIP1	ENST00000352523.10	c.*413T>G		3_prime_UTR_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13352 AN: 152164 Hom.: 775 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.121 AC: 1098 AN: 9062 Hom.: 73 Cov.: 0 AF XY: 0.122 AC XY: 560 AN XY: 4590

Gnomad4 AFR exome AF: 0.0271

Gnomad4 AMR exome AF: 0.0551

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.00930

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0877 AC: 13352 AN: 152282 Hom.: 774 Cov.: 32 AF XY: 0.0867 AC XY: 6457 AN XY: 74454

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0898

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.103

Alfa AF: 0.121 Hom.: 1459

Bravo AF: 0.0811

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.62

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: rs8543; hg19: chr5-172591337;