Variant 8-7470360-G-C 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_001040702.1(DEFB104B):c.215C>G(p.Pro72Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 7)

Exomes 𝑓: 0.00045 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DEFB104B
NM_001040702.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.00

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062083006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB104B	NM_001040702.1 linkuse as main transcript	c.215C>G	p.Pro72Arg	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.215C>G	p.Pro72Arg	missense_variant	2/2	1	NM_001040702.1	ENSP00000322191.2		Q8WTQ1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

139

AN:

58484

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00858

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

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:

0.0000349

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000724

AC:

AN:

4146

Hom.:

AF XY:

0.00

AC XY:

AN XY:

2366

show subpopulations

Gnomad AFR exome

AF:

0.0224

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000449

AC:

AN:

73538

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

37200

show subpopulations

Gnomad4 AFR exome

AF:

0.00985

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:

0.0000215

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00243

AC:

142

AN:

58480

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

AN XY:

25466

show subpopulations

Gnomad4 AFR

AF:

0.00874

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000349

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000931

Hom.:

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

Apr 25, 2022

The c.215C>G (p.P72R) alteration is located in exon 2 (coding exon 2) of the DEFB104B gene. This alteration results from a C to G substitution at nucleotide position 215, causing the proline (P) at amino acid position 72 to be replaced by an arginine (R). 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

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.4

DANN

Benign

0.96

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0036

M_CAP

Benign

0.00094

MetaRNN

Benign

0.0062

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.0060

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.083

MutPred

0.41

Gain of MoRF binding (P = 2e-04);

MVP

0.16

ClinPred

0.038

GERP RS

-3.8

gMVP

0.040

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