Genetic Variant BRICD5:p.Arg128His (chr16-2210005-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182563.4(BRICD5):c.383G>A(p.Arg128His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,560,330 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000099 ( 1 hom. )

Consequence

BRICD5
NM_182563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.08

Variant links:

Genes affected

BRICD5 (HGNC:28309): (BRICHOS domain containing 5) Predicted to be involved in regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BRICD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015897185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRICD5	NM_182563.4 link	c.383G>A	p.Arg128His	missense_variant	Exon 4 of 6	ENST00000328540.8	NP_872369.2	Q6PL45-2
BRICD5	XM_047433958.1 link	c.383G>A	p.Arg128His	missense_variant	Exon 4 of 5		XP_047289914.1
BRICD5	XM_047433959.1 link	c.449G>A	p.Arg150His	missense_variant	Exon 2 of 4		XP_047289915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BRICD5	ENST00000328540.8 link	c.383G>A	p.Arg128His	missense_variant	Exon 4 of 6	1	NM_182563.4	ENSP00000332389.3	Q6PL45-2
BRICD5	ENST00000562360.5 link	c.383G>A	p.Arg128His	missense_variant	Exon 4 of 5	2		ENSP00000455052.1	Q6PL45-1
BRICD5	ENST00000566018.1 link	c.457G>A	p.Ala153Thr	missense_variant	Exon 3 of 3	2		ENSP00000457969.1	H3BV65
BRICD5	ENST00000566795.1 link	n.141G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000131

AC:

AN:

213466

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

114576

show subpopulations

Gnomad AFR exome

AF:

0.0000653

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000154

Gnomad EAS exome

AF:

0.000283

Gnomad SAS exome

AF:

0.000720

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000414

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000987

AC:

139

AN:

1408138

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

693020

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000439

Gnomad4 EAS exome

AF:

0.000154

Gnomad4 SAS exome

AF:

0.000869

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000528

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000413

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.383G>A (p.R128H) alteration is located in exon 4 (coding exon 4) of the BRICD5 gene. This alteration results from a G to A substitution at nucleotide position 383, causing the arginine (R) at amino acid position 128 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.27

M_CAP

Benign

0.027

MetaRNN

Benign

0.016

PROVEAN

Benign

1.2

Sift

Pathogenic

0.0

Vest4

0.11

MVP

0.28

ClinPred

0.043

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over