rs10503786

Variant names:

• chr8-26412420-C-T
• rs10503786
• NM_004331.3:c.*2008C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BNIP3L	NM_004331.3	c.*2008C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000380629.7	NP_004322.1
BNIP3L	NM_001330491.2	c.*2008C>T		3_prime_UTR_variant	Exon 6 of 6		NP_001317420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNIP3L	ENST00000380629.7	c.*2008C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_004331.3	ENSP00000370003.2
BNIP3L	ENST00000523949.5	c.545+4044C>T		intron_variant	Intron 5 of 5	3		ENSP00000429171.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0907 AC: 3768 AN: 41534

American (AMR) AF: 0.221 AC: 3377 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3466

East Asian (EAS) AF: 0.172 AC: 887 AN: 5166

South Asian (SAS) AF: 0.253 AC: 1223 AN: 4826

European-Finnish (FIN) AF: 0.372 AC: 3927 AN: 10548

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21564 AN: 67974

Other (OTH) AF: 0.232 AC: 491 AN: 2116

Alfa AF: 0.288 Hom.: 3918

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
PhyloP100		0.30
Mutation Taster		=100/0	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: rs10503786; hg19: chr8-26269936;