11-71833244-C-A

Position:

chr11-71833244-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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:

XNDC1N-ZNF705EP-ALG1L9P (HGNC:):

XNDC1N-ZNF705EP-ALG1L9P links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25973505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB108B	NM_001002035.2 linkuse as main transcript	c.45C>A	p.Ser15Arg	missense_variant	1/2	ENST00000328698.2	NP_001002035.1	Q8NET1
XNDC1N-ZNF705EP-ALG1L9P	NR_172893.1 linkuse as main transcript	n.708-6617G>T		intron_variant
XNDC1N-ZNF705EP-ALG1L9P	NR_172894.1 linkuse as main transcript	n.875-11697G>T		intron_variant
XNDC1N-ZNF705EP-ALG1L9P	NR_172895.1 linkuse as main transcript	n.1000-11697G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DEFB108B	ENST00000328698.2 linkuse as main transcript	c.45C>A	p.Ser15Arg	missense_variant	1/2	1	NM_001002035.2	ENSP00000333234.1	Q8NET1
XNDC1N-ZNF705EP-ALG1L9P	ENST00000696863.1 linkuse as main transcript	n.700-6617G>T		intron_variant				ENSP00000512936.1	A0A8Q3WLN7
XNDC1N-ZNF705EP-ALG1L9P	ENST00000696864.1 linkuse as main transcript	n.523-11697G>T		intron_variant				ENSP00000512937.1	A0A8Q3WLL2
XNDC1N-ZNF705EP-ALG1L9P	ENST00000696865.1 linkuse as main transcript	n.*243-11697G>T		intron_variant				ENSP00000512938.1	E9PLZ0

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

GnomAD3 exomes

AF:

0.0000481

AC:

AN:

228456

Hom.:

AF XY:

0.0000646

AC XY:

AN XY:

123894

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 SAS exome

AF:

0.000386

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000485

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.18e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000663

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.45C>A (p.S15R) alteration is located in exon 1 (coding exon 1) of the DEFB108B gene. This alteration results from a C to A substitution at nucleotide position 45, causing the serine (S) at amino acid position 15 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

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

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

Varity_R

0.39

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over