Genetic Variant DEFB113:p.Arg39His (chr6-49968810-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037729.1(DEFB113):c.116G>A(p.Arg39His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,602,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

DEFB113
NM_001037729.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.569

Publications

3 publications found

Variant links:

Genes affected

DEFB113 (HGNC:18094): (defensin beta 113) 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. [provided by RefSeq, Oct 2014]

DEFB113 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08050266).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037729.1. 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
	DEFB113	NM_001037729.1	MANE Select	c.116G>A	p.Arg39His	missense	Exon 2 of 2	NP_001032818.1	Q30KQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB113	ENST00000398718.1	TSL:1 MANE Select	c.116G>A	p.Arg39His	missense	Exon 2 of 2	ENSP00000381703.1	Q30KQ7

Frequencies

GnomAD3 genomes

AF:

0.0000662

AC:

AN:

151020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000872

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000500

AC:

AN:

240238

AF XY:

0.0000613

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000812

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000364

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1451948

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

722042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32672

American (AMR)

AF:

0.00

AC:

AN:

43366

Ashkenazi Jewish (ASJ)

AF:

0.000580

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39206

South Asian (SAS)

AF:

0.0000237

AC:

AN:

84448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

1107492

Other (OTH)

AF:

0.0000501

AC:

AN:

59878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000662

AC:

AN:

151020

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73732

show subpopulations

African (AFR)

AF:

0.0000969

AC:

AN:

41292

American (AMR)

AF:

0.00

AC:

AN:

15082

Ashkenazi Jewish (ASJ)

AF:

0.000872

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000446

AC:

AN:

67326

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000858

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.46

M_CAP

Benign

0.0045

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.93

PhyloP100

-0.57

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.018

Sift

Uncertain

0.014

Sift4G

Uncertain

0.035

Polyphen

0.47

Vest4

0.27

MVP

0.16

MPC

0.0073

ClinPred

0.25

GERP RS

0.38

Varity_R

0.15

gMVP

0.40

Mutation Taster

=91/9

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over