Variant chr8-11994062-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001302695.2(DEFB134):c.119T>A(p.Leu40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 33)

Consequence

DEFB134
NM_001302695.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32792547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB134	NM_001302695.2 linkuse as main transcript	c.119T>A	p.Leu40His	missense_variant	3/3	ENST00000382205.6	NP_001289624.1	Q4QY38
DEFB134	XM_017013724.1 linkuse as main transcript	c.119T>A	p.Leu40His	missense_variant	3/3		XP_016869213.1	Q4QY38
DEFB134	XM_047422075.1 linkuse as main transcript	c.119T>A	p.Leu40His	missense_variant	2/2		XP_047278031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB134	ENST00000382205.6 linkuse as main transcript	c.119T>A	p.Leu40His	missense_variant	3/3	1	NM_001302695.2	ENSP00000371640.4		Q4QY38
DEFB134	ENST00000526438.6 linkuse as main transcript	c.119T>A	p.Leu40His	missense_variant	2/2	1		ENSP00000435010.1		Q4QY38

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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 08, 2023

The c.119T>A (p.L40H) alteration is located in exon 2 (coding exon 2) of the DEFB134 gene. This alteration results from a T to A substitution at nucleotide position 119, causing the leucine (L) at amino acid position 40 to be replaced by a histidine (H). 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

0.25

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.038

M_CAP

Benign

0.0019

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.9

D;.

REVEL

Benign

0.083

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.98

D;D

Vest4

0.53

MutPred

0.36

Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);

MVP

0.18

MPC

0.00067

ClinPred

0.63

GERP RS

2.4

Varity_R

0.42

gMVP

0.49

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