6-50019086-C-T

Variant summary

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

The NM_001037497.2(DEFB110):​c.95G>A​(p.Arg32Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DEFB110
NM_001037497.2 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.556
Variant links:
Genes affected
DEFB110 (HGNC:18091): (defensin beta 110) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 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=0.0568372).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEFB110NM_001037497.2 linkc.95G>A p.Arg32Lys missense_variant 2/2 ENST00000371148.3 NP_001032586.1 Q30KQ9-1
DEFB110NM_001037728.2 linkc.55+2795G>A intron_variant NP_001032817.1 Q30KQ9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEFB110ENST00000371148.3 linkc.95G>A p.Arg32Lys missense_variant 2/21 NM_001037497.2 ENSP00000360190.2 Q30KQ9-1
DEFB110ENST00000393660.2 linkc.55+2795G>A intron_variant 1 ENSP00000377270.2 Q30KQ9-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250672
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135512
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460914
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726758
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 30, 2024The c.95G>A (p.R32K) alteration is located in exon 2 (coding exon 2) of the DEFB110 gene. This alteration results from a G to A substitution at nucleotide position 95, causing the arginine (R) at amino acid position 32 to be replaced by a lysine (K). 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
0.18
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
14
DANN
Benign
0.95
DEOGEN2
Benign
0.051
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.012
Sift
Benign
0.076
T
Sift4G
Benign
0.13
T
Polyphen
0.23
B
Vest4
0.26
MutPred
0.30
Gain of ubiquitination at R32 (P = 0.017);
MVP
0.048
MPC
0.0023
ClinPred
0.48
T
GERP RS
1.8
Varity_R
0.11
gMVP
0.43

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: rs755318636; hg19: chr6-49986799; COSMIC: COSV100953807; API