1-151043051-C-T

Variant names:

• chr1-151043051-C-T
• rs200082390
• NM_138278.4:c.529C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138278.4(BNIPL):​c.529C>T​(p.His177Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: BNIPL NM_138278.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14423418).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138278.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIPL	NM_138278.4	MANE Select	c.529C>T	p.His177Tyr	missense	Exon 5 of 10	NP_612122.2	Q7Z465-1
	BNIPL	NM_001159642.2		c.283C>T	p.His95Tyr	missense	Exon 5 of 10	NP_001153114.1	Q7Z465-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIPL	ENST00000368931.8	TSL:1 MANE Select	c.529C>T	p.His177Tyr	missense	Exon 5 of 10	ENSP00000357927.3	Q7Z465-1
	BNIPL	ENST00000295294.11	TSL:1	c.283C>T	p.His95Tyr	missense	Exon 5 of 10	ENSP00000295294.7	Q7Z465-2
	BNIPL	ENST00000912274.1		c.529C>T	p.His177Tyr	missense	Exon 5 of 10	ENSP00000582333.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248750 AF XY: 0.00000744

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000354 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.17
Sift	Benign	0.26	T
Sift4G	Benign	0.092	T
Polyphen		0.39	B
Vest4		0.20
MVP		0.61
MPC		0.52
ClinPred		0.18	T
GERP RS		5.3
Varity_R		0.068
gMVP		0.17
Mutation Taster		=92/8	polymorphism

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: rs200082390; hg19: chr1-151015527;