chr20-31389161-C-T

Variant summary

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

The NM_153323.5(DEFB119):​c.131G>A​(p.Arg44Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 32)
Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

DEFB119
NM_153323.5 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.11
Variant links:
Genes affected
DEFB119 (HGNC:18099): (defensin beta 119) This gene encodes a member of the beta subfamily of defensins. Beta-defensins are antimicrobial peptides that protect tissues and organs from infection by a variety of microorganisms. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [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=0.019611686).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DEFB119NM_153289.4 linkc.61+1262G>A intron_variant Intron 1 of 1 ENST00000376321.4 NP_695021.2 Q8N690-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEFB119ENST00000376315.2 linkc.131G>A p.Arg44Gln missense_variant Exon 2 of 2 1 ENSP00000365492.2 Q8N690-2
DEFB119ENST00000376321.4 linkc.61+1262G>A intron_variant Intron 1 of 1 1 NM_153289.4 ENSP00000365499.3 Q8N690-1
DEFB119ENST00000339144.3 linkc.61+1262G>A intron_variant Intron 1 of 2 1 ENSP00000345768.3 Q8N690-3
DEFB119ENST00000492344.1 linkn.148-802G>A intron_variant Intron 1 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000596
AC:
15
AN:
251488
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.000198
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000650
AC:
95
AN:
1461892
Hom.:
0
Cov.:
35
AF XY:
0.0000605
AC XY:
44
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000710
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000494
Hom.:
0
Bravo
AF:
0.0000264
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000218
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.131G>A (p.R44Q) alteration is located in exon 2 (coding exon 2) of the DEFB119 gene. This alteration results from a G to A substitution at nucleotide position 131, causing the arginine (R) at amino acid position 44 to be replaced by a glutamine (Q). 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
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
7.7
DANN
Benign
0.96
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0031
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.020
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.75
N
REVEL
Benign
0.013
Sift
Benign
0.11
T
Sift4G
Benign
0.12
T
Polyphen
0.014
B
Vest4
0.18
MVP
0.040
MPC
0.14
ClinPred
0.043
T
GERP RS
-7.4
gMVP
0.34

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: rs181386606; hg19: chr20-29976964; COSMIC: COSV59265555; API