1-177255967-C-G

Position:

• chr1-177255967-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021165.4(BRINP2):​c.318C>G​(p.Asp106Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BRINP2 NM_021165.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.510

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]

LOC105371625 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05874008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP2	NM_021165.4	c.318C>G	p.Asp106Glu	missense_variant	3/8	ENST00000361539.5	NP_066988.1
BRINP2	XM_005245379.3	c.318C>G	p.Asp106Glu	missense_variant	4/9		XP_005245436.1
BRINP2	XM_024448722.2	c.318C>G	p.Asp106Glu	missense_variant	4/9		XP_024304490.1
LOC105371625	XR_922299.4	n.73G>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP2	ENST00000361539.5	c.318C>G	p.Asp106Glu	missense_variant	3/8	1	NM_021165.4	ENSP00000354481.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Nov 23, 2021

The c.318C>G (p.D106E) alteration is located in exon 3 (coding exon 2) of the BRINP2 gene. This alteration results from a C to G substitution at nucleotide position 318, causing the aspartic acid (D) at amino acid position 106 to be replaced by a glutamic acid (E). 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	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.28
Sift	Benign	0.083	T
Sift4G	Benign	0.20	T
Polyphen		0.019	B
Vest4		0.24
MutPred		0.38		Loss of sheet (P = 0.0063);
MVP		0.12
MPC		0.29
ClinPred		0.45	T
GERP RS		2.3
Varity_R		0.11
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1571935019; hg19: chr1-177225103;