1-190243735-G-C

Variant names:

• chr1-190243735-G-C
• rs12140456
• NM_199051.3:c.619-9258C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199051.3(BRINP3):​c.619-9258C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,956 control chromosomes in the GnomAD database, including 12,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (12586 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 1 publications found

Genes affected

BRINP3 (HGNC:22393): (BMP/retinoic acid inducible neural specific 3) This gene is overexpressed in pituitary tumors but is underexpressed in tongue squamous cell carcinomas, ulcerative colitis, and peri-implantitis. Polymorphisms that increase expression of this gene have been shown to increase vascular inflammation, and an association of this gene with myocardial infarction has been demonstrated. Finally, hypermethylation of this gene may find usefulness as a biomarker for gastric cancer. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

LOC105371659 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199051.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP3	NM_199051.3	MANE Select	c.619-9258C>G		intron	N/A	NP_950252.1
	BRINP3	NM_001317188.2		c.313-9258C>G		intron	N/A	NP_001304117.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP3	ENST00000367462.5	TSL:1 MANE Select	c.619-9258C>G		intron	N/A	ENSP00000356432.3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58336 AN: 151838 Hom.: 12592 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.384 AC: 58326 AN: 151956 Hom.: 12586 Cov.: 32 AF XY: 0.383 AC XY: 28438 AN XY: 74252

African (AFR) AF: 0.170 AC: 7045 AN: 41490

American (AMR) AF: 0.467 AC: 7113 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.384 AC: 1971 AN: 5130

South Asian (SAS) AF: 0.372 AC: 1794 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4553 AN: 10564

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33000 AN: 67932

Other (OTH) AF: 0.406 AC: 856 AN: 2108

Alfa AF: 0.298 Hom.: 888

Bravo AF: 0.377

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.33
DANN	Benign	0.64
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs12140456; hg19: chr1-190212865;