Genetic Variant DEFB128:p.His62ThrfsTer5 (chr20-187984-G-GT) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001037732.3(DEFB128):c.183dupA(p.His62ThrfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 1,613,820 control chromosomes in the GnomAD database, including 763 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.030 ( 67 hom., cov: 31)

Exomes 𝑓: 0.029 ( 696 hom. )

Consequence

DEFB128
NM_001037732.3 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.932

Variant links:

Genes affected

DEFB128 (HGNC:18106): (defensin beta 128) 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 20p13. [provided by RefSeq, Nov 2014]

DEFB128 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 20-187984-G-GT is Benign according to our data. Variant chr20-187984-G-GT is described in ClinVar as [Likely_benign]. Clinvar id is 3057209.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0303 (4612/152192) while in subpopulation AFR AF= 0.0388 (1610/41528). AF 95% confidence interval is 0.0372. There are 67 homozygotes in gnomad4. There are 2308 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB128	NM_001037732.3 link	c.183dupA	p.His62ThrfsTer5	frameshift_variant	Exon 2 of 2	ENST00000334391.5	NP_001032821.1	Q7Z7B8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB128	ENST00000334391.5 link	c.183dupA	p.His62ThrfsTer5	frameshift_variant	Exon 2 of 2	1	NM_001037732.3	ENSP00000335382.4		Q7Z7B8

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4612

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.0261

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0309

Gnomad FIN

AF:

0.0308

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0288

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0265

AC:

6648

AN:

251146

Hom.:

129

AF XY:

0.0268

AC XY:

3644

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0390

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0297

Gnomad FIN exome

AF:

0.0301

Gnomad NFE exome

AF:

0.0325

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0285

AC:

41670

AN:

1461628

Hom.:

696

Cov.:

AF XY:

0.0283

AC XY:

20572

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0378

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.00995

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.0294

Gnomad4 FIN exome

AF:

0.0300

Gnomad4 NFE exome

AF:

0.0302

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.0303

AC:

4612

AN:

152192

Hom.:

Cov.:

AF XY:

0.0310

AC XY:

2308

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0388

Gnomad4 AMR

AF:

0.0260

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0307

Gnomad4 FIN

AF:

0.0308

Gnomad4 NFE

AF:

0.0288

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0277

Hom.:

Bravo

AF:

0.0291

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DEFB128-related disorder

Benign:1

Nov 01, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

20-187984-GT-GTT

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