Variant 8-7415020-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BP4_Strong

The NM_001205266.2(DEFB4B):c.136A>G(p.Arg46Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEFB4B
NM_001205266.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.81

Variant links:

Genes affected

DEFB4B (HGNC:30193): (defensin beta 4B) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 4, an antibiotic peptide which is locally regulated by inflammation. [provided by RefSeq, Oct 2014]

DEFB4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM1

In a mutagenesis_site No impact on fungal cell permeabilization. Impaired antifungal activity. (size 0) in uniprot entity DFB4A_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.035879046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB4B	NM_001205266.2 linkuse as main transcript	c.136A>G	p.Arg46Gly	missense_variant	2/2	ENST00000318157.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB4B	ENST00000318157.3 linkuse as main transcript	c.136A>G	p.Arg46Gly	missense_variant	2/2	1	NM_001205266.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147800

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00102

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:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000151

AC:

AN:

1261614

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

631412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000505

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000101

AC:

AN:

147914

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

AN XY:

72006

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00102

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:

0.00

ExAC

AF:

0.00000894

AC:

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 submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.136A>G (p.R46G) alteration is located in exon 2 (coding exon 2) of the DEFB4B gene. This alteration results from a A to G substitution at nucleotide position 136, causing the arginine (R) at amino acid position 46 to be replaced by a glycine (G). 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

-0.64

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0080

DANN

Benign

0.32

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0020

M_CAP

Benign

0.00044

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

0.63

REVEL

Benign

0.015

Sift

Benign

0.48

Sift4G

Benign

0.48

Vest4

0.087

MutPred

0.47

Loss of stability (P = 0.0254);

MVP

0.23

ClinPred

0.023

GERP RS

-3.9

gMVP

0.053

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over