NM_021165.4:c.763G>A

Variant names:

• chr1-177273581-G-A
• rs370267758
• NM_021165.4:c.763G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021165.4(BRINP2):​c.763G>A​(p.Val255Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,583,956 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V255L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BRINP2 NM_021165.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

BRINP2 (HGNC:13746): (BMP/retinoic acid inducible neural specific 2) Predicted to be involved in cellular response to retinoic acid; negative regulation of mitotic cell cycle; and positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in dendrite; endoplasmic reticulum; and neuronal cell body. Implicated in oral squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06073177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021165.4. 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
	BRINP2	NM_021165.4	MANE Select	c.763G>A	p.Val255Ile	missense	Exon 5 of 8	NP_066988.1	Q9C0B6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP2	ENST00000361539.5	TSL:1 MANE Select	c.763G>A	p.Val255Ile	missense	Exon 5 of 8	ENSP00000354481.4	Q9C0B6-1
	BRINP2	ENST00000944009.1		c.814G>A	p.Val272Ile	missense	Exon 5 of 8	ENSP00000614068.1
	BRINP2	ENST00000907915.1		c.763G>A	p.Val255Ile	missense	Exon 6 of 9	ENSP00000577974.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151356 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000431 AC: 1 AN: 231974 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: 0.00000937

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1432600 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 712888

African (AFR) AF: 0.00 AC: 0 AN: 31980

American (AMR) AF: 0.00 AC: 0 AN: 41576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25122

East Asian (EAS) AF: 0.00 AC: 0 AN: 37964

South Asian (SAS) AF: 0.00 AC: 0 AN: 82378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5396

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1096406

Other (OTH) AF: 0.00 AC: 0 AN: 58814

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151356 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73804

African (AFR) AF: 0.00 AC: 0 AN: 41158

American (AMR) AF: 0.00 AC: 0 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.83
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
PhyloP100		2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.045
Sift	Benign	1.0	T
Sift4G	Benign	0.58	T
Polyphen		0.0090	B
Vest4		0.23
MVP		0.043
MPC		0.21
ClinPred		0.14	T
GERP RS		5.4
Varity_R		0.024
gMVP		0.23
Mutation Taster		=93/7	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: rs370267758; hg19: chr1-177242717; COSMIC: COSV100838145;