chr1-177230040-T-G

Position:

• chr1-177230040-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021165.4(BRINP2):​c.164T>G​(p.Leu55Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BRINP2 NM_021165.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP2	NM_021165.4	c.164T>G	p.Leu55Arg	missense_variant	2/8	ENST00000361539.5	NP_066988.1
BRINP2	XM_005245379.3	c.164T>G	p.Leu55Arg	missense_variant	3/9		XP_005245436.1
BRINP2	XM_024448722.2	c.164T>G	p.Leu55Arg	missense_variant	3/9		XP_024304490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP2	ENST00000361539.5	c.164T>G	p.Leu55Arg	missense_variant	2/8	1	NM_021165.4	ENSP00000354481.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461504 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.164T>G (p.L55R) alteration is located in exon 2 (coding exon 1) of the BRINP2 gene. This alteration results from a T to G substitution at nucleotide position 164, causing the leucine (L) at amino acid position 55 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.66
MVP		0.21
MPC		1.1
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.64
gMVP		0.87

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-177199176;