chr1-177219115-G-A

Variant names:

• chr1-177219115-G-A
• rs566442
• NM_021165.4:c.-76-10686G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BRINP2	NM_021165.4	c.-76-10686G>A		intron_variant	Intron 1 of 7	ENST00000361539.5	NP_066988.1
BRINP2	XM_005245379.3	c.-77+9405G>A		intron_variant	Intron 2 of 8		XP_005245436.1
BRINP2	XM_024448722.2	c.-77+9405G>A		intron_variant	Intron 2 of 8		XP_024304490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP2	ENST00000361539.5	c.-76-10686G>A		intron_variant	Intron 1 of 7	1	NM_021165.4	ENSP00000354481.4

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

African (AFR) AF: 0.977 AC: 40626 AN: 41568

American (AMR) AF: 0.934 AC: 14288 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3215 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5175 AN: 5182

South Asian (SAS) AF: 0.964 AC: 4656 AN: 4828

European-Finnish (FIN) AF: 0.764 AC: 8093 AN: 10588

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58524 AN: 68000

Other (OTH) AF: 0.933 AC: 1974 AN: 2116

Alfa AF: 0.902 Hom.: 23880

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
PhyloP100		-0.20
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: rs566442; hg19: chr1-177188251;