Variant 8-7896534-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_004942.4(DEFB4A):c.119C>T(p.Pro40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 2)

Exomes 𝑓: 0.0060 ( 183 hom. )

Failed GnomAD Quality Control

Consequence

DEFB4A
NM_004942.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0100

Variant links:

Genes affected

DEFB4A (HGNC:2767): (defensin beta 4A) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 4, an antibiotic peptide which is locally regulated by inflammation. [provided by RefSeq, Jul 2008]

DEFB4A 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=0.011950821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB4A	NM_004942.4 linkuse as main transcript	c.119C>T	p.Pro40Leu	missense_variant	2/2	ENST00000302247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB4A	ENST00000302247.3 linkuse as main transcript	c.119C>T	p.Pro40Leu	missense_variant	2/2	1	NM_004942.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

13458

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00480

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00622

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00423

AC:

AN:

11830

Hom.:

AF XY:

0.00507

AC XY:

AN XY:

6110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00691

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00758

Gnomad OTH exome

AF:

0.00521

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00597

AC:

937

AN:

156916

Hom.:

183

Cov.:

AF XY:

0.00581

AC XY:

475

AN XY:

81732

show subpopulations

Gnomad4 AFR exome

AF:

0.000787

Gnomad4 AMR exome

AF:

0.00838

Gnomad4 ASJ exome

AF:

0.0151

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00285

Gnomad4 NFE exome

AF:

0.00745

Gnomad4 OTH exome

AF:

0.00546

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00290

AC:

AN:

13464

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

AN XY:

5896

show subpopulations

Gnomad4 AFR

AF:

0.000305

Gnomad4 AMR

AF:

0.00479

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00623

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00354

Hom.:

ExAC

AF:

0.00208

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

Sep 01, 2021

The c.119C>T (p.P40L) alteration is located in exon 2 (coding exon 2) of the DEFB4A gene. This alteration results from a C to T substitution at nucleotide position 119, causing the proline (P) at amino acid position 40 to be replaced by a leucine (L). 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

0.34

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.3

DANN

Benign

0.79

DEOGEN2

Benign

0.052

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0027

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-6.6

REVEL

Benign

0.070

Sift

Uncertain

0.021

Sift4G

Benign

0.67

Polyphen

0.27

Vest4

0.20

MutPred

0.88

Loss of disorder (P = 0.1769);

MVP

0.014

MPC

1.2

ClinPred

0.047

GERP RS

0.010

Varity_R

0.19

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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