chr1-190270777-A-G

Variant names:

• chr1-190270777-A-G
• rs10920678
• NM_199051.3:c.428-5722T>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.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
• Publications: 19 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]

ENSG00000225811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.428-5722T>C		intron	N/A	NP_950252.1
	BRINP3	NM_001317188.2		c.122-5722T>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.428-5722T>C		intron	N/A	ENSP00000356432.3
	BRINP3	ENST00000631494.1	TSL:4	c.428-5722T>C		intron	N/A	ENSP00000487601.1
	ENSG00000225811	ENST00000452178.1	TSL:5	n.142+5738A>G		intron	N/A

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

African (AFR) AF: 0.591 AC: 24417 AN: 41346

American (AMR) AF: 0.693 AC: 10497 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2274 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3306 AN: 5136

South Asian (SAS) AF: 0.642 AC: 3098 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4869 AN: 10516

Middle Eastern (MID) AF: 0.621 AC: 180 AN: 290

European-Non Finnish (NFE) AF: 0.568 AC: 38295 AN: 67460

Other (OTH) AF: 0.623 AC: 1313 AN: 2106

Alfa AF: 0.586 Hom.: 13428

Bravo AF: 0.605

Asia WGS AF: 0.655 AC: 2267 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.61
PhyloP100		0.26
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: rs10920678; hg19: chr1-190239907;