chr1-177276417-G-C

Variant names:

• chr1-177276417-G-C
• rs147553727
• NM_021165.4:c.995G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021165.4(BRINP2):​c.995G>C​(p.Arg332Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R332Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: BRINP2 NM_021165.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19841954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP2	NM_021165.4	c.995G>C	p.Arg332Pro	missense_variant	Exon 6 of 8	ENST00000361539.5	NP_066988.1
BRINP2	XM_005245379.3	c.995G>C	p.Arg332Pro	missense_variant	Exon 7 of 9		XP_005245436.1
BRINP2	XM_024448722.2	c.995G>C	p.Arg332Pro	missense_variant	Exon 7 of 9		XP_024304490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP2	ENST00000361539.5	c.995G>C	p.Arg332Pro	missense_variant	Exon 6 of 8	1	NM_021165.4	ENSP00000354481.4
BRINP2	ENST00000478325.1	n.851G>C		non_coding_transcript_exon_variant	Exon 3 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248650 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134480

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000205 AC: 3 AN: 1461798 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.099
Sift	Benign	0.084	T
Sift4G	Benign	0.072	T
Polyphen		0.34	B
Vest4		0.63
MutPred		0.25		Gain of glycosylation at T329 (P = 0.0218);
MVP		0.068
MPC		0.36
ClinPred		0.35	T
GERP RS		2.1
Varity_R		0.56
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs147553727; hg19: chr1-177245553;