rs1194111996

Variant names:

• chr5-173151572-C-T
• rs1194111996
• ENST00000231668.13:c.184C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013979.3(BNIP1):​c.184C>T​(p.Leu62Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BNIP1 NM_013979.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.884
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059454173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013979.3. 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
	BNIP1	NM_001205.3	MANE Select	c.178-2750C>T		intron	N/A	NP_001196.2	Q12981-4
	BNIP1	NM_013979.3		c.184C>T	p.Leu62Phe	missense	Exon 3 of 7	NP_053582.2	Q12981-1
	BNIP1	NM_013980.3		c.184C>T	p.Leu62Phe	missense	Exon 3 of 6	NP_053583.2	Q12981-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP1	ENST00000231668.13	TSL:1	c.184C>T	p.Leu62Phe	missense	Exon 3 of 7	ENSP00000231668.9	Q12981-1
	BNIP1	ENST00000352523.10	TSL:1	c.184C>T	p.Leu62Phe	missense	Exon 3 of 6	ENSP00000239214.8	Q12981-3
	BNIP1	ENST00000351486.10	TSL:1 MANE Select	c.178-2750C>T		intron	N/A	ENSP00000239215.7	Q12981-4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 144676 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00000892 AC: 2 AN: 224254 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000956

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000922 AC: 13 AN: 1409944 Hom.: 0 Cov.: 35 AF XY: 0.00000570 AC XY: 4 AN XY: 701426

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30904

American (AMR) AF: 0.000135 AC: 5 AN: 36936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24662

East Asian (EAS) AF: 0.00 AC: 0 AN: 38774

South Asian (SAS) AF: 0.0000377 AC: 3 AN: 79602

European-Finnish (FIN) AF: 0.0000204 AC: 1 AN: 49128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5216

European-Non Finnish (NFE) AF: 0.00000276 AC: 3 AN: 1086650

Other (OTH) AF: 0.0000172 AC: 1 AN: 58072

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 144676 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 69974

African (AFR) AF: 0.00 AC: 0 AN: 39114

American (AMR) AF: 0.00 AC: 0 AN: 14426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4964

South Asian (SAS) AF: 0.00 AC: 0 AN: 4606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8792

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66180

Other (OTH) AF: 0.00 AC: 0 AN: 1992

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	0.098
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.9
DANN	Uncertain	0.98
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.88
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.034
Sift	Benign	0.18	T
Sift4G	Benign	0.32	T
Polyphen		0.0020	B
Vest4		0.067
MutPred		0.23		Loss of helix (P = 0.079)
MVP		0.22
MPC		0.34
ClinPred		0.024	T
GERP RS		0.24
gMVP		0.080
Mutation Taster		=100/0	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: rs1194111996; hg19: chr5-172578575;