Genetic Variant DEFB107A:p.Val9Ile (chr8-7815604-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_001037668.1(DEFB107A):c.25G>A(p.Val9Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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. V9F) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000082 ( 0 hom., cov: 16)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEFB107A
NM_001037668.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.151

Publications

5 publications found

Variant links:

Genes affected

DEFB107A (HGNC:18086): (defensin beta 107A) 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. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 107, DEFB107A and DEFB107B, in tail-to-tail orientation. This gene, DEFB107A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

DEFB107A links:

LOC124901865 (HGNC:):

LOC124901865 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=0.07013348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037668.1. 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
	DEFB107A	NM_001037668.1	MANE Select	c.25G>A	p.Val9Ile	missense	Exon 1 of 2	NP_001032757.2	Q8IZN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB107A	ENST00000335021.2	TSL:1 MANE Select	c.25G>A	p.Val9Ile	missense	Exon 1 of 2	ENSP00000334681.2	Q8IZN7

Frequencies

GnomAD3 genomes

AF:

0.00000825

AC:

AN:

121246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

806206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

414870

African (AFR)

AF:

0.00

AC:

AN:

19006

American (AMR)

AF:

0.00

AC:

AN:

27526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17112

East Asian (EAS)

AF:

0.00

AC:

AN:

33082

South Asian (SAS)

AF:

0.00

AC:

AN:

58570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

562396

Other (OTH)

AF:

0.00

AC:

AN:

37170

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000824

AC:

AN:

121378

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

58266

show subpopulations

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

African (AFR)

AF:

0.0000303

AC:

AN:

33034

American (AMR)

AF:

0.00

AC:

AN:

11458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2886

East Asian (EAS)

AF:

0.00

AC:

AN:

3602

South Asian (SAS)

AF:

0.00

AC:

AN:

3086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57108

Other (OTH)

AF:

0.00

AC:

AN:

1490

⚠️ 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: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.5

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0050

M_CAP

Benign

0.010

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

PhyloP100

0.15

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.60

REVEL

Benign

0.0070

Sift

Benign

0.17

Sift4G

Benign

0.28

Vest4

0.033

MutPred

0.31

Loss of ubiquitination at K6 (P = 0.1403)

MVP

0.49

ClinPred

0.42

GERP RS

-0.041

PromoterAI

0.0012

Neutral

(source)

Varity_R

0.029

gMVP

0.061

Mutation Taster

=100/0

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

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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