rs1053081

Positions:

• chr1-190097855-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_199051.3(BRINP3):​c.*163T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 742,570 control chromosomes in the GnomAD database, including 51 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 0.0080 (12 hom., cov: 32)
  • Exomes 𝑓: 0.010 (39 hom.)
• Consequence: BRINP3 NM_199051.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.*163T>C		3_prime_UTR_variant	8/8	ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.*163T>C		3_prime_UTR_variant	8/8	1	NM_199051.3	ENSP00000356432	P1

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 1215 AN: 152176 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00475

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0102 AC: 6009 AN: 590276 Hom.: 39 Cov.: 8 AF XY: 0.0103 AC XY: 3135 AN XY: 304920

Gnomad4 AFR exome AF: 0.00229

Gnomad4 AMR exome AF: 0.00775

Gnomad4 ASJ exome AF: 0.00763

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00494

Gnomad4 FIN exome AF: 0.00322

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.00965

GnomAD4 genome AF: 0.00798 AC: 1215 AN: 152294 Hom.: 12 Cov.: 32 AF XY: 0.00765 AC XY: 570 AN XY: 74478

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00980 Hom.: 1

Bravo AF: 0.00777

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.90

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: rs1053081; hg19: chr1-190066985;