1-190105748-A-G

Variant names:

• chr1-190105748-A-G
• rs10800889
• NM_199051.3:c.1185-6614T>C

Variant summary

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

The NM_199051.3(BRINP3):​c.1185-6614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,714 control chromosomes in the GnomAD database, including 21,970 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 0.53 (21970 hom., cov: 31)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 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.1185-6614T>C		intron	N/A	NP_950252.1
	BRINP3	NM_001317188.2		c.879-6614T>C		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.1185-6614T>C		intron	N/A	ENSP00000356432.3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80608 AN: 151596 Hom.: 21935 Cov.: 31

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.532 AC: 80686 AN: 151714 Hom.: 21970 Cov.: 31 AF XY: 0.529 AC XY: 39228 AN XY: 74160

African (AFR) AF: 0.625 AC: 25889 AN: 41396

American (AMR) AF: 0.401 AC: 6091 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1853 AN: 3456

East Asian (EAS) AF: 0.372 AC: 1920 AN: 5166

South Asian (SAS) AF: 0.545 AC: 2622 AN: 4810

European-Finnish (FIN) AF: 0.543 AC: 5728 AN: 10556

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34778 AN: 67836

Other (OTH) AF: 0.522 AC: 1096 AN: 2100

Alfa AF: 0.516 Hom.: 5041

Bravo AF: 0.521

Asia WGS AF: 0.471 AC: 1634 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-0.24
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: rs10800889; hg19: chr1-190074878;