chr7-98282362-C-G

Variant names:

• chr7-98282362-C-G
• rs979069467
• NM_015379.5:c.154C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015379.5(BRI3):​c.154C>G​(p.His52Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H52Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: BRI3 NM_015379.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

Genes affected

BRI3 (HGNC:1109): (brain protein I3) Enables identical protein binding activity. Predicted to be located in azurophil granule membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12175271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015379.5. 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
	BRI3	NM_015379.5	MANE Select	c.154C>G	p.His52Asp	missense	Exon 2 of 3	NP_056194.1	O95415-1
	BRI3	NM_001159491.2		c.154C>G	p.His52Asp	missense	Exon 2 of 3	NP_001152963.1	O95415-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRI3	ENST00000297290.4	TSL:1 MANE Select	c.154C>G	p.His52Asp	missense	Exon 2 of 3	ENSP00000297290.3	O95415-1
	BRI3	ENST00000539286.5	TSL:2	c.154C>G	p.His52Asp	missense	Exon 2 of 3	ENSP00000440936.1	O95415-2
	BRI3	ENST00000456357.6	TSL:2	n.162C>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461640 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.044
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.0050	B
Vest4		0.45
MutPred		0.31		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.14
MPC		0.50
ClinPred		0.13	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.67
Mutation Taster		=88/12	polymorphism

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: rs979069467; hg19: chr7-97911674;