rs10920725

Variant names:

• chr1-190471407-T-C
• rs10920725
• NM_199051.3:c.-51+6041A>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.-51+6041A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,090 control chromosomes in the GnomAD database, including 3,551 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 0.21 (3551 hom., cov: 32)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP3	NM_199051.3	MANE Select	c.-51+6041A>G		intron	N/A	NP_950252.1	Q76B58-1
	BRINP3	NM_001317188.2		c.-166+4373A>G		intron	N/A	NP_001304117.1	Q76B58-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRINP3	ENST00000367462.5	TSL:1 MANE Select	c.-51+6041A>G		intron	N/A	ENSP00000356432.3	Q76B58-1
	BRINP3	ENST00000956272.1		c.-51+4891A>G		intron	N/A	ENSP00000626331.1
	BRINP3	ENST00000631494.1	TSL:4	c.-51+4373A>G		intron	N/A	ENSP00000487601.1	A0A0J9YVN8

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32283 AN: 150972 Hom.: 3540 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.214 AC: 32327 AN: 151090 Hom.: 3551 Cov.: 32 AF XY: 0.215 AC XY: 15842 AN XY: 73834

African (AFR) AF: 0.241 AC: 9994 AN: 41438

American (AMR) AF: 0.196 AC: 2969 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3454

East Asian (EAS) AF: 0.181 AC: 936 AN: 5170

South Asian (SAS) AF: 0.243 AC: 1172 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2377 AN: 10524

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13431 AN: 67204

Other (OTH) AF: 0.180 AC: 377 AN: 2100

Alfa AF: 0.205 Hom.: 440

Bravo AF: 0.211

Asia WGS AF: 0.198 AC: 683 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.83
PhyloP100		-0.0070
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: rs10920725; hg19: chr1-190440537; COSMIC: COSV107472773;