Genetic Variant DEFB4B:p.Gly26Asp (chr8-7415079-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001205266.2(DEFB4B):c.77G>A(p.Gly26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G26A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEFB4B
NM_001205266.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0882687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205266.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB4B	NM_001205266.2	MANE Select	c.77G>A	p.Gly26Asp	missense	Exon 2 of 2	NP_001192195.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB4B	ENST00000318157.3	TSL:1 MANE Select	c.77G>A	p.Gly26Asp	missense	Exon 2 of 2	ENSP00000424598.1	O15263

Frequencies

GnomAD3 genomes

AF:

0.00000679

AC:

AN:

147350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

968604

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

487552

African (AFR)

AF:

0.00

AC:

AN:

21992

American (AMR)

AF:

0.00

AC:

AN:

26570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19184

East Asian (EAS)

AF:

0.00

AC:

AN:

33750

South Asian (SAS)

AF:

0.00

AC:

AN:

61098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3130

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

712582

Other (OTH)

AF:

0.00

AC:

AN:

43010

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000679

AC:

AN:

147350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71604

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

39200

American (AMR)

AF:

0.00

AC:

AN:

14566

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.000196

AC:

AN:

5112

South Asian (SAS)

AF:

0.00

AC:

AN:

4506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67144

Other (OTH)

AF:

0.00

AC:

AN:

1950

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.020

(source)

DANN

Benign

0.48

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0017

M_CAP

Benign

0.00057

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.99

PhyloP100

-2.3

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.72

REVEL

Benign

0.025

Sift

Benign

0.70

Sift4G

Benign

0.62

Vest4

0.16

MutPred

0.29

Loss of catalytic residue at G24 (P = 0.0947)

MVP

0.030

ClinPred

0.026

GERP RS

-2.8

gMVP

0.073

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over