rs566442

chr1-177219115-G-A

Variant summary

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

The NM_021165.4(BRINP2):c.-76-10686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,256 control chromosomes in the GnomAD database, including 62,648 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 0.90 (62648 hom., cov: 33)
• Consequence: BRINP2 NM_021165.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

Genes affected

BRINP2 (HGNC:13746): (BMP/retinoic acid inducible neural specific 2) Predicted to be involved in cellular response to retinoic acid; negative regulation of mitotic cell cycle; and positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in dendrite; endoplasmic reticulum; and neuronal cell body. Implicated in oral squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRINP2	NM_021165.4	c.-76-10686G>A		intron_variant		ENST00000361539.5
BRINP2	XM_005245379.3	c.-77+9405G>A		intron_variant
BRINP2	XM_024448722.2	c.-77+9405G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRINP2	ENST00000361539.5	c.-76-10686G>A		intron_variant		1	NM_021165.4	P1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137596 AN: 152138 Hom.: 62587 Cov.: 33

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.932

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

GnomAD4 genome AF: 0.905 AC: 137716 AN: 152256 Hom.: 62648 Cov.: 33 AF XY: 0.903 AC XY: 67232 AN XY: 74426

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.933

Alfa AF: 0.885 Hom.: 8925

Bravo AF: 0.921

Asia WGS AF: 0.985 AC: 3425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.23
Dann	Benign	0.47

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: rs566442; hg19: chr1-177188251;