Variant 8-7828943-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_152251.4(DEFB106A):c.188T>G(p.Ile63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,321,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000089 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEFB106A
NM_152251.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.91

Variant links:

Genes affected

DEFB106A (HGNC:18088): (defensin beta 106A) 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. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 106, DEFB106A and DEFB106B, in head-to-head orientation. This gene, DEFB106A, represents the more centromeric copy. [provided by RefSeq, Oct 2014]

DEFB106A links:

LOC124901865 (HGNC:):

LOC124901865 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04382202).

BP6

Variant 8-7828943-T-G is Benign according to our data. Variant chr8-7828943-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2224968.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB106A	NM_152251.4 linkuse as main transcript	c.188T>G	p.Ile63Ser	missense_variant	2/2	ENST00000335186.3	NP_689464.1	Q8N104
LOC124901865	use as main transcript	n.7828943T>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB106A	ENST00000335186.3 linkuse as main transcript	c.188T>G	p.Ile63Ser	missense_variant	2/2	1	NM_152251.4	ENSP00000335307.2		Q8N104

Frequencies

GnomAD3 genomes

AF:

0.0000626

AC:

AN:

143700

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000107

Gnomad OTH

AF:

0.000528

GnomAD3 exomes

AF:

0.00000794

AC:

AN:

126014

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66108

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000886

AC:

117

AN:

1321276

Hom.:

Cov.:

AF XY:

0.0000843

AC XY:

AN XY:

652214

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.0000369

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000626

AC:

AN:

143700

Hom.:

Cov.:

AF XY:

0.0000431

AC XY:

AN XY:

69626

show subpopulations

Gnomad4 AFR

AF:

0.0000258

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000107

Gnomad4 OTH

AF:

0.000528

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00000872

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0010

DANN

Benign

0.52

DEOGEN2

Benign

0.0055

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.00071

M_CAP

Benign

0.00048

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

1.7

REVEL

Benign

0.016

Sift

Benign

0.73

Sift4G

Benign

0.21

Vest4

0.17

MVP

0.014

MPC

2.5

ClinPred

0.037

GERP RS

-6.4

Varity_R

0.036

gMVP

0.14

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