Genetic Variant DEFB134:p.Lys30Asn (chr8-11994091-C-G) – 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_001302695.2(DEFB134):c.90G>C(p.Lys30Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

DEFB134
NM_001302695.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.150

Publications

1 publications found

Variant links:

Genes affected

DEFB134 (HGNC:32399): (defensin beta 134) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The antimicrobial protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 8p23. [provided by RefSeq, Nov 2014]

DEFB134 links:

ENSG00000290829 (HGNC:):

ENSG00000290829 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=0.13564771).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302695.2. 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
	DEFB134	NM_001302695.2	MANE Select	c.90G>C	p.Lys30Asn	missense	Exon 3 of 3	NP_001289624.1	Q4QY38

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEFB134	ENST00000382205.6	TSL:1 MANE Select	c.90G>C	p.Lys30Asn	missense	Exon 3 of 3	ENSP00000371640.4	Q4QY38
DEFB134	ENST00000526438.6	TSL:1	c.90G>C	p.Lys30Asn	missense	Exon 2 of 2	ENSP00000435010.1	Q4QY38
ENSG00000290829	ENST00000715792.1		n.365G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152156

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250568

AF XY:

0.00000738

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461114

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86138

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111772

Other (OTH)

AF:

0.00

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.0000263

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000165

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

Uncertain

0.35

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.1

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.016

M_CAP

Benign

0.0013

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

PhyloP100

-0.15

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.018

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.020

Polyphen

0.84

Vest4

0.21

MutPred

0.23

Loss of methylation at K30 (P = 0.0242)

MVP

0.20

MPC

0.00067

ClinPred

0.29

GERP RS

1.4

Varity_R

0.18

gMVP

0.45

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over