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

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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

GnomAD2 exomes

AF:

0.0265

AC:

6648

AN:

251146

AF XY:

0.0268

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 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

African (AFR)

AF:

0.0378

AC:

1265

AN:

33464

American (AMR)

AF:

0.0143

AC:

641

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00995

AC:

260

AN:

26130

East Asian (EAS)

AF:

0.000655

AC:

AN:

39692

South Asian (SAS)

AF:

0.0294

AC:

2537

AN:

86256

European-Finnish (FIN)

AF:

0.0300

AC:

1600

AN:

53418

Middle Eastern (MID)

AF:

0.0250

AC:

144

AN:

5766

European-Non Finnish (NFE)

AF:

0.0302

AC:

33576

AN:

1111788

Other (OTH)

AF:

0.0268

AC:

1621

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

2512

5024

7535

10047

12559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1216

2432

3648

4864

6080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0303

AC:

4612

AN:

152192

Hom.:

Cov.:

AF XY:

0.0310

AC XY:

2308

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0388

AC:

1610

AN:

41528

American (AMR)

AF:

0.0260

AC:

398

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00894

AC:

AN:

3466

East Asian (EAS)

AF:

0.000965

AC:

AN:

5182

South Asian (SAS)

AF:

0.0307

AC:

148

AN:

4818

European-Finnish (FIN)

AF:

0.0308

AC:

327

AN:

10600

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0288

AC:

1955

AN:

67992

Other (OTH)

AF:

0.0265

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

225

450

674

899

1124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

PhyloP100

-0.93

Mutation Taster

=194/6

polymorphism (auto)

(source)

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

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20-187984-GT-GTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over