1-190270777-A-G

Position:

• chr1-190270777-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199051.3(BRINP3):​c.428-5722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,204 control chromosomes in the GnomAD database, including 26,188 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 0.59 (26188 hom., cov: 31)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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]

ENSG00000225811 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.428-5722T>C		intron_variant		ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.428-5722T>C		intron_variant		1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.428-5722T>C		intron_variant		4		ENSP00000487601.1
ENSG00000225811	ENST00000452178.1	n.142+5738A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88558 AN: 151088 Hom.: 26152 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.612

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.586 AC: 88644 AN: 151204 Hom.: 26188 Cov.: 31 AF XY: 0.585 AC XY: 43230 AN XY: 73844

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.623

Alfa AF: 0.586 Hom.: 11938

Bravo AF: 0.605

Asia WGS AF: 0.655 AC: 2267 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.61

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: rs10920678; hg19: chr1-190239907;