20-188116-C-T

Variant summary

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

The NM_001037732.3(DEFB128):​c.52G>A​(p.Gly18Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

DEFB128
NM_001037732.3 missense, splice_region

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.366
Variant links:
Genes affected
DEFB128 (HGNC:18106): (defensin beta 128) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The antimicrobial protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20p13. [provided by RefSeq, Nov 2014]

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=0.035723984).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DEFB128NM_001037732.3 linkc.52G>A p.Gly18Arg missense_variant, splice_region_variant Exon 2 of 2 ENST00000334391.5 NP_001032821.1 Q7Z7B8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEFB128ENST00000334391.5 linkc.52G>A p.Gly18Arg missense_variant, splice_region_variant Exon 2 of 2 1 NM_001037732.3 ENSP00000335382.4 Q7Z7B8

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152100
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250724
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135534
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
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:
0.00000958
AC:
14
AN:
1461336
Hom.:
0
Cov.:
34
AF XY:
0.00000688
AC XY:
5
AN XY:
727012
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152100
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.52G>A (p.G18R) alteration is located in exon 2 (coding exon 2) of the DEFB128 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the glycine (G) at amino acid position 18 to be replaced by an arginine (R). 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
0.19
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.036
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.022
Sift
Benign
0.14
T
Sift4G
Benign
0.33
T
Polyphen
0.078
B
Vest4
0.11
MutPred
0.30
Gain of solvent accessibility (P = 0.0306);
MVP
0.043
MPC
0.040
ClinPred
0.052
T
GERP RS
-2.6
Varity_R
0.044
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs753697132; hg19: chr20-168757; API