chr1-190473841-G-A

Variant names:

• chr1-190473841-G-A
• rs2490271
• NM_199051.3:c.-51+3607C>T

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+3607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 150,600 control chromosomes in the GnomAD database, including 46,367 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 0.78 (46367 hom., cov: 27)
• Consequence: BRINP3 NM_199051.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP3	NM_199051.3	c.-51+3607C>T		intron_variant	Intron 1 of 7	ENST00000367462.5	NP_950252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP3	ENST00000367462.5	c.-51+3607C>T		intron_variant	Intron 1 of 7	1	NM_199051.3	ENSP00000356432.3
BRINP3	ENST00000631494.1	c.-51+1939C>T		intron_variant	Intron 1 of 3	4		ENSP00000487601.1
BRINP3	ENST00000445957.2	c.-51+567C>T		intron_variant	Intron 1 of 1	3		ENSP00000393441.2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 117910 AN: 150502 Hom.: 46340 Cov.: 27

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.779

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.783 AC: 117978 AN: 150600 Hom.: 46367 Cov.: 27 AF XY: 0.784 AC XY: 57620 AN XY: 73452

African (AFR) AF: 0.726 AC: 29701 AN: 40932

American (AMR) AF: 0.784 AC: 11883 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2878 AN: 3460

East Asian (EAS) AF: 0.683 AC: 3475 AN: 5090

South Asian (SAS) AF: 0.767 AC: 3682 AN: 4800

European-Finnish (FIN) AF: 0.828 AC: 8389 AN: 10126

Middle Eastern (MID) AF: 0.774 AC: 223 AN: 288

European-Non Finnish (NFE) AF: 0.818 AC: 55428 AN: 67742

Other (OTH) AF: 0.780 AC: 1625 AN: 2084

Alfa AF: 0.809 Hom.: 77133

Bravo AF: 0.774

Asia WGS AF: 0.711 AC: 2469 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.32
PhyloP100		-0.17
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: rs2490271; hg19: chr1-190442971;