4-9444586-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040448.3(DEFB131A):​c.53C>T​(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,577,836 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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. P18S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000067 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

DEFB131A
NM_001040448.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0170
Variant links:
Genes affected
DEFB131A (HGNC:18108): (defensin beta 131A) 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 4p16. [provided by RefSeq, Nov 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07892606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DEFB131ANM_001040448.3 linkc.53C>T p.Pro18Leu missense_variant Exon 1 of 2 ENST00000334879.2 NP_001035538.2 P59861

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DEFB131AENST00000334879.2 linkc.53C>T p.Pro18Leu missense_variant Exon 1 of 2 1 NM_001040448.3 ENSP00000335538.1 P59861

Frequencies

GnomAD3 genomes
AF:
0.0000673
AC:
8
AN:
118910
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000539
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000101
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:
0.0000972
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000591
AC:
14
AN:
236908
Hom.:
0
AF XY:
0.0000854
AC XY:
11
AN XY:
128748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.000129
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000113
AC:
165
AN:
1458926
Hom.:
0
Cov.:
29
AF XY:
0.0000937
AC XY:
68
AN XY:
725780
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000140
Gnomad4 OTH exome
AF:
0.000150
GnomAD4 genome
AF:
0.0000673
AC:
8
AN:
118910
Hom.:
1
Cov.:
33
AF XY:
0.0000348
AC XY:
2
AN XY:
57528
show subpopulations
Gnomad4 AFR
AF:
0.0000539
Gnomad4 AMR
AF:
0.000101
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000972
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000988
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000414
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 09, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.53C>T (p.P18L) alteration is located in exon 1 (coding exon 1) of the DEFB131 gene. This alteration results from a C to T substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by a leucine (L). 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
0.12
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
14
DANN
Benign
0.95
DEOGEN2
Benign
0.090
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0015
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.00062
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Benign
0.053
Sift
Benign
0.31
T
Sift4G
Benign
0.34
T
Polyphen
0.0080
B
Vest4
0.29
MVP
0.014
MPC
0.00037
ClinPred
0.054
T
GERP RS
-0.74
Varity_R
0.068
gMVP
0.071

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: rs777237570; hg19: chr4-9446312; API