rs10503786

Positions:

• chr8-26412420-C-T

Variant summary

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

The NM_004331.3(BNIP3L):​c.*2008C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,110 control chromosomes in the GnomAD database, including 5,172 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 0.24 (5172 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: BNIP3L NM_004331.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

Genes affected

BNIP3L (HGNC:1085): (BCL2 interacting protein 3 like) This gene encodes a protein that belongs to the pro-apoptotic subfamily within the Bcl-2 family of proteins. The encoded protein binds to Bcl-2 and possesses the BH3 domain. The protein directly targets mitochondria and causes apoptotic changes, including loss of membrane potential and the release of cytochrome c. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP3L	NM_004331.3	c.*2008C>T		3_prime_UTR_variant	6/6	ENST00000380629.7	NP_004322.1
BNIP3L	NM_001330491.2	c.*2008C>T		3_prime_UTR_variant	6/6		NP_001317420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIP3L	ENST00000380629.7	c.*2008C>T		3_prime_UTR_variant	6/6	1	NM_004331.3	ENSP00000370003	P1
BNIP3L	ENST00000523949.5	c.545+4044C>T		intron_variant		3		ENSP00000429171

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36072 AN: 151992 Hom.: 5169 Cov.: 33

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.233

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.237 AC: 36081 AN: 152110 Hom.: 5172 Cov.: 33 AF XY: 0.240 AC XY: 17823 AN XY: 74326

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.232

Alfa AF: 0.289 Hom.: 3543

Bravo AF: 0.217

Asia WGS AF: 0.200 AC: 695 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.21

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: rs10503786; hg19: chr8-26269936;