Variant chr20-259226-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207469.3(DEFB132):c.208C>T(p.Leu70Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,612,392 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

DEFB132
NM_207469.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.611

Variant links:

Genes affected

DEFB132 (HGNC:33806): (defensin beta 132) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The protein encoded by this gene is secreted and is a member of the beta defensin protein family. This protein binds spermatozoa and has antimicrobial activity against E. coli. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20p13. [provided by RefSeq, Nov 2014]

DEFB132 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074810684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB132	NM_207469.3 linkuse as main transcript	c.208C>T	p.Leu70Phe	missense_variant	2/2	ENST00000382376.4	NP_997352.1	Q7Z7B7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB132	ENST00000382376.4 linkuse as main transcript	c.208C>T	p.Leu70Phe	missense_variant	2/2	1	NM_207469.3	ENSP00000371813.3		Q7Z7B7

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD3 exomes

AF:

0.0000954

AC:

AN:

251478

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000589

AC:

AN:

1460210

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726438

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000342

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000645

Hom.:

Bravo

AF:

0.000370

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Oct 16, 2024

The c.208C>T (p.L70F) alteration is located in exon 2 (coding exon 2) of the DEFB132 gene. This alteration results from a C to T substitution at nucleotide position 208, causing the leucine (L) at amino acid position 70 to be replaced by a phenylalanine (F). 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

Benign

0.086

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0053

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.39

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.55

REVEL

Benign

0.015

Sift

Benign

0.30

Sift4G

Benign

0.22

Polyphen

0.35

Vest4

0.033

MVP

0.061

MPC

0.042

ClinPred

0.0076

GERP RS

-0.27

Varity_R

0.071

gMVP

0.024

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

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