rs774359125

Variant names:

Variant summary

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

The NM_001002035.2(DEFB108B):c.45C>A(p.Ser15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,583,508 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 1 hom. )

Consequence

DEFB108B
NM_001002035.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

0 publications found

Variant links:

Genes affected

DEFB108B (HGNC:29966): (defensin beta 108B) 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. A pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Oct 2014]

DEFB108B links:

XNDC1N-ZNF705EP-ALG1L9P (HGNC:55871): (XNDC1N-ZNF705EP-ALG1L9P readthrough) This locus represents naturally occurring readthrough transcription between the neighboring XNDC1N (XRCC1 N-terminal domain containing 1-like), ZNF705P (zinc finger protein 705, pseudogene) and ALG1L9P (ALG1 like 9, pseudogene) genes on chromosome 11q13.4. These readthrough transcripts are candidates for nonsense-mediated mRNA decay (NMD), and are unlikely to produce a protein product. [provided by RefSeq, Aug 2021]

XNDC1N-ZNF705EP-ALG1L9P links:

Genome browser will be placed here

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=0.25973505).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002035.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEFB108B	NM_001002035.2	MANE Select	c.45C>A	p.Ser15Arg	missense	Exon 1 of 2	NP_001002035.1	Q8NET1
XNDC1N-ZNF705EP-ALG1L9P	NR_172893.1		n.708-6617G>T		intron	N/A
XNDC1N-ZNF705EP-ALG1L9P	NR_172894.1		n.875-11697G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEFB108B	ENST00000328698.2	TSL:1 MANE Select	c.45C>A	p.Ser15Arg	missense	Exon 1 of 2	ENSP00000333234.1	Q8NET1
XNDC1N-ZNF705EP-ALG1L9P	ENST00000696863.1		n.700-6617G>T		intron	N/A	ENSP00000512936.1	A0A8Q3WLN7
XNDC1N-ZNF705EP-ALG1L9P	ENST00000696864.1		n.523-11697G>T		intron	N/A	ENSP00000512937.1	A0A8Q3WLL2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152128

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:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000481

AC:

AN:

228456

AF XY:

0.0000646

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000293

AC:

AN:

1431380

Hom.:

Cov.:

AF XY:

0.0000379

AC XY:

AN XY:

712788

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32662

American (AMR)

AF:

0.00

AC:

AN:

43824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25704

East Asian (EAS)

AF:

0.00

AC:

AN:

39600

South Asian (SAS)

AF:

0.000485

AC:

AN:

84506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4064

European-Non Finnish (NFE)

AF:

9.18e-7

AC:

AN:

1088908

Other (OTH)

AF:

0.00

AC:

AN:

59108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.401

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:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00

Hom.:

ExAC

AF:

0.0000663

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

0.46

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.020

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.45

M_CAP

Benign

0.0038

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

PhyloP100

1.5

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.58

MutPred

0.35

Gain of MoRF binding (P = 0.0182)

MVP

0.11

MPC

0.39

ClinPred

0.44

GERP RS

1.5

PromoterAI

-0.0030

Neutral

(source)

Varity_R

0.39

gMVP

0.36

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over