Genetic Variant DEFB127:p.Thr18Thr (chr20-158778-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_139074.4(DEFB127):c.54C>T(p.Thr18Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,609,612 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0040 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 132 hom. )

Consequence

DEFB127
NM_139074.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

5 publications found

Variant links:

Genes affected

DEFB127 (HGNC:16206): (defensin beta 127) 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]

DEFB127 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-1.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB127	NM_139074.4 link	c.54C>T	p.Thr18Thr	synonymous_variant	Exon 2 of 2	ENST00000382388.4	NP_620713.1	Q9H1M4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB127	ENST00000382388.4 link	c.54C>T	p.Thr18Thr	synonymous_variant	Exon 2 of 2	1	NM_139074.4	ENSP00000371825.3		Q9H1M4

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

610

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0724

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00675

AC:

1670

AN:

247490

AF XY:

0.00647

show subpopulations

Gnomad AFR exome

AF:

0.00397

Gnomad AMR exome

AF:

0.000297

Gnomad ASJ exome

AF:

0.00164

Gnomad EAS exome

AF:

0.0739

Gnomad FIN exome

AF:

0.00103

Gnomad NFE exome

AF:

0.000909

Gnomad OTH exome

AF:

0.00517

GnomAD4 exome

AF:

0.00305

AC:

4442

AN:

1457458

Hom.:

132

Cov.:

AF XY:

0.00308

AC XY:

2235

AN XY:

725012

show subpopulations

African (AFR)

AF:

0.00389

AC:

129

AN:

33188

American (AMR)

AF:

0.000364

AC:

AN:

43922

Ashkenazi Jewish (ASJ)

AF:

0.00178

AC:

AN:

25850

East Asian (EAS)

AF:

0.0788

AC:

3124

AN:

39656

South Asian (SAS)

AF:

0.00273

AC:

234

AN:

85694

European-Finnish (FIN)

AF:

0.00105

AC:

AN:

53232

Middle Eastern (MID)

AF:

0.000873

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.000416

AC:

462

AN:

1110050

Other (OTH)

AF:

0.00615

AC:

370

AN:

60140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

223

446

670

893

1116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.00403

AC:

613

AN:

152154

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

346

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00393

AC:

163

AN:

41500

American (AMR)

AF:

0.000524

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.0727

AC:

377

AN:

5184

South Asian (SAS)

AF:

0.00312

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

67996

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00173

Hom.:

Bravo

AF:

0.00481

Asia WGS

AF:

0.0360

AC:

123

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.2

(source)

DANN

Benign

0.64

PhyloP100

-1.9

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over