Variant 8-7470462-C-T 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.113G>A(p.Arg38Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.058 ( 0 hom., cov: 2)

Exomes 𝑓: 0.12 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

DEFB104B
NM_001040702.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0830

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=0.0026998222).

BP6

Variant 8-7470462-C-T is Benign according to our data. Variant chr8-7470462-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2213576.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.113G>A	p.Arg38Gln	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.113G>A	p.Arg38Gln	missense_variant	2/2	1	NM_001040702.1	ENSP00000322191.2		Q8WTQ1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

404

AN:

6918

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00665

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0920

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.0659

Gnomad SAS

AF:

0.0672

Gnomad FIN

AF:

0.0926

Gnomad MID

AF:

0.0455

Gnomad NFE

AF:

0.0801

Gnomad OTH

AF:

0.0673

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.119

AC:

20783

AN:

174696

Hom.:

Cov.:

AF XY:

0.117

AC XY:

10673

AN XY:

90916

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.0939

Gnomad4 SAS exome

AF:

0.0970

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0583

AC:

404

AN:

6926

Hom.:

Cov.:

AF XY:

0.0603

AC XY:

172

AN XY:

2854

show subpopulations

Gnomad4 AFR

AF:

0.00659

Gnomad4 AMR

AF:

0.0938

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.0659

Gnomad4 SAS

AF:

0.0639

Gnomad4 FIN

AF:

0.0926

Gnomad4 NFE

AF:

0.0802

Gnomad4 OTH

AF:

0.0686

Alfa

AF:

0.0739

Hom.:

ExAC

AF:

0.00943

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

Sep 16, 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

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.025

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.014

Sift

Benign

0.051

Sift4G

Pathogenic

0.0

Vest4

0.20

ClinPred

0.038

GERP RS

1.2

gMVP

0.17

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