16-2209972-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_182563.4(BRICD5):​c.416G>A​(p.Arg139Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000202 in 1,535,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

BRICD5
NM_182563.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.558
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.039886743).
BP6
Variant 16-2209972-C-T is Benign according to our data. Variant chr16-2209972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2396022.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRICD5NM_182563.4 linkc.416G>A p.Arg139Gln missense_variant Exon 4 of 6 ENST00000328540.8 NP_872369.2 Q6PL45-2
BRICD5XM_047433958.1 linkc.416G>A p.Arg139Gln missense_variant Exon 4 of 5 XP_047289914.1
BRICD5XM_047433959.1 linkc.482G>A p.Arg161Gln missense_variant Exon 2 of 4 XP_047289915.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRICD5ENST00000328540.8 linkc.416G>A p.Arg139Gln missense_variant Exon 4 of 6 1 NM_182563.4 ENSP00000332389.3 Q6PL45-2
BRICD5ENST00000562360.5 linkc.416G>A p.Arg139Gln missense_variant Exon 4 of 5 2 ENSP00000455052.1 Q6PL45-1
BRICD5ENST00000566795.1 linkn.174G>A non_coding_transcript_exon_variant Exon 1 of 2 3
BRICD5ENST00000566018.1 linkc.*28G>A downstream_gene_variant 2 ENSP00000457969.1 H3BV65

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000317
AC:
6
AN:
189400
Hom.:
0
AF XY:
0.00000993
AC XY:
1
AN XY:
100706
show subpopulations
Gnomad AFR exome
AF:
0.0000672
Gnomad AMR exome
AF:
0.000194
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000195
AC:
27
AN:
1382780
Hom.:
0
Cov.:
33
AF XY:
0.0000177
AC XY:
12
AN XY:
678266
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000141
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000103
Gnomad4 SAS exome
AF:
0.0000134
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000140
Gnomad4 OTH exome
AF:
0.0000352
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000214
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000167
AC:
2
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 14, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
0.048
DANN
Benign
0.82
DEOGEN2
Benign
0.0034
.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0095
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.040
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
-1.0
N;N
PrimateAI
Benign
0.18
T
PROVEAN
Benign
0.51
N;N
REVEL
Benign
0.16
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.033
B;B
Vest4
0.28
MutPred
0.23
Loss of phosphorylation at T137 (P = 0.1701);Loss of phosphorylation at T137 (P = 0.1701);
MVP
0.45
MPC
0.0024
ClinPred
0.019
T
GERP RS
-6.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.019
gMVP
0.17

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.

Other links and lift over

dbSNP: rs376368009; hg19: chr16-2259973; COSMIC: COSV57026215; COSMIC: COSV57026215; API