1-151038849-C-T

Position:

• chr1-151038849-C-T

Variant summary

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

The NM_138278.4(BNIPL):​c.256C>T​(p.Arg86Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,130 control chromosomes in the GnomAD database, including 15,263 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 0.095 (965 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14298 hom.)
• Consequence: BNIPL NM_138278.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

Genes affected

BNIPL (HGNC:16976): (BCL2 interacting protein like) The protein encoded by this gene interacts with several other proteins, such as BCL2, ARHGAP1, MIF and GFER. It may function as a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

BNIPL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017173588).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIPL	NM_138278.4	c.256C>T	p.Arg86Cys	missense_variant	4/10	ENST00000368931.8	NP_612122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIPL	ENST00000368931.8	c.256C>T	p.Arg86Cys	missense_variant	4/10	1	NM_138278.4	ENSP00000357927.3

Frequencies

GnomAD3 genomes AF: 0.0956 AC: 14544 AN: 152194 Hom.: 965 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0666

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.100

GnomAD3 exomes AF: 0.0991 AC: 24820 AN: 250470 Hom.: 1578 AF XY: 0.102 AC XY: 13797 AN XY: 135410

Gnomad AFR exome AF: 0.0210

Gnomad AMR exome AF: 0.0497

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0706

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.0964

GnomAD4 exome AF: 0.133 AC: 194981 AN: 1460818 Hom.: 14298 Cov.: 32 AF XY: 0.132 AC XY: 95874 AN XY: 726688

Gnomad4 AFR exome AF: 0.0194

Gnomad4 AMR exome AF: 0.0520

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0729

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0955 AC: 14541 AN: 152312 Hom.: 965 Cov.: 32 AF XY: 0.0917 AC XY: 6831 AN XY: 74490

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.000962

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.131 Hom.: 2485

Bravo AF: 0.0899

TwinsUK AF: 0.157 AC: 582

ALSPAC AF: 0.154 AC: 594

ESP6500AA AF: 0.0306 AC: 135

ESP6500EA AF: 0.142 AC: 1221

ExAC AF: 0.0999 AC: 12129

Asia WGS AF: 0.0330 AC: 117 AN: 3478

EpiCase AF: 0.141

EpiControl AF: 0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	.;T;.;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	.;T;T;D
MetaRNN	Benign	0.0017	T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.6	.;M;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.0	.;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Pathogenic	0.0010	.;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.13, 0.39
MPC		1.2
ClinPred		0.021	T
GERP RS		5.2
Varity_R		0.36
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs61751619; hg19: chr1-151011325;