5-173144562-A-G

Variant names:

• chr5-173144562-A-G
• rs371311208
• NM_001205.3:c.17A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001205.3(BNIP1):​c.17A>G​(p.Asp6Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D6N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: BNIP1 NM_001205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• 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]

ENSG00000253172 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11028606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205.3. 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.17A>G	p.Asp6Gly	missense	Exon 1 of 6	NP_001196.2	Q12981-4
	BNIP1	NM_013979.3		c.17A>G	p.Asp6Gly	missense	Exon 1 of 7	NP_053582.2	Q12981-1
	BNIP1	NM_013980.3		c.17A>G	p.Asp6Gly	missense	Exon 1 of 6	NP_053583.2	Q12981-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP1	ENST00000351486.10	TSL:1 MANE Select	c.17A>G	p.Asp6Gly	missense	Exon 1 of 6	ENSP00000239215.7	Q12981-4
	BNIP1	ENST00000231668.13	TSL:1	c.17A>G	p.Asp6Gly	missense	Exon 1 of 7	ENSP00000231668.9	Q12981-1
	BNIP1	ENST00000352523.10	TSL:1	c.17A>G	p.Asp6Gly	missense	Exon 1 of 6	ENSP00000239214.8	Q12981-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000716 AC: 18 AN: 251232 AF XY: 0.0000810

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000434

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 AF: 0.0000144 AC: 21 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000335 AC: 15 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

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	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.018	D
Polyphen		0.98	D
Vest4		0.40
MVP		0.69
MPC		1.1
ClinPred		0.57	D
GERP RS		5.1
PromoterAI		-0.017	Neutral
Varity_R		0.51
gMVP		0.65
Mutation Taster		=62/38	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: rs371311208; hg19: chr5-172571565;