Variant 8-7470469-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001040702.1(DEFB104B):c.106C>T(p.Arg36Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.024 ( 0 hom., cov: 2)

Exomes 𝑓: 0.047 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

DEFB104B
NM_001040702.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.64

Variant links:

Genes affected

DEFB104B (HGNC:26165): (defensin beta 104B) 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 104, DEFB104A and DEFB104B, in head-to-head orientation. This gene, DEFB104B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

DEFB104B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028290749).

BP6

Variant 8-7470469-G-A is Benign according to our data. Variant chr8-7470469-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2205652.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB104B	NM_001040702.1 linkuse as main transcript	c.106C>T	p.Arg36Cys	missense_variant	2/2	ENST00000316169.2	NP_001035792.1	Q8WTQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB104B	ENST00000316169.2 linkuse as main transcript	c.106C>T	p.Arg36Cys	missense_variant	2/2	1	NM_001040702.1	ENSP00000322191.2		Q8WTQ1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

137

AN:

5630

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.0556

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00427

Gnomad FIN

AF:

0.0909

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0114

GnomAD3 exomes

AF:

0.0332

AC:

659

AN:

19824

Hom.:

AF XY:

0.0322

AC XY:

343

AN XY:

10644

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.0383

Gnomad ASJ exome

AF:

0.0595

Gnomad EAS exome

AF:

0.000335

Gnomad SAS exome

AF:

0.00712

Gnomad FIN exome

AF:

0.0833

Gnomad NFE exome

AF:

0.0540

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0467

AC:

8303

AN:

177734

Hom.:

Cov.:

AF XY:

0.0447

AC XY:

4134

AN XY:

92396

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.0412

Gnomad4 ASJ exome

AF:

0.0638

Gnomad4 EAS exome

AF:

0.0000983

Gnomad4 SAS exome

AF:

0.00708

Gnomad4 FIN exome

AF:

0.0636

Gnomad4 NFE exome

AF:

0.0570

Gnomad4 OTH exome

AF:

0.0530

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0243

AC:

137

AN:

5634

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

AN XY:

2320

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.0295

Gnomad4 ASJ

AF:

0.0556

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00431

Gnomad4 FIN

AF:

0.0909

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.0116

ExAC

AF:

0.00581

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

Apr 28, 2022

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

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.099

Eigen_PC

Benign

-0.076

FATHMM_MKL

Benign

0.54

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.3

REVEL

Benign

0.15

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Vest4

0.35

MutPred

0.36

Loss of MoRF binding (P = 0.0094);

ClinPred

0.049

GERP RS

2.1

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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