dbSNP rs16995685: DEFB127:p.Arg71Ser (chr20-158935-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139074.4(DEFB127):c.211C>A(p.Arg71Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,613,014 control chromosomes in the GnomAD database, including 104,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 7939 hom., cov: 32)

Exomes 𝑓: 0.36 ( 96911 hom. )

Consequence

DEFB127
NM_139074.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.601

Publications

35 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.723282E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB127	NM_139074.4 link	c.211C>A	p.Arg71Ser	missense_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.211C>A	p.Arg71Ser	missense_variant	Exon 2 of 2	1	NM_139074.4	ENSP00000371825.3		Q9H1M4

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44587

AN:

151906

Hom.:

7944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0890

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.292

GnomAD2 exomes

AF:

0.369

AC:

92297

AN:

250332

AF XY:

0.376

show subpopulations

Gnomad AFR exome

AF:

0.0809

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.377

Gnomad EAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.346

GnomAD4 exome

AF:

0.358

AC:

523641

AN:

1460990

Hom.:

96911

Cov.:

AF XY:

0.362

AC XY:

263005

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.0746

AC:

2496

AN:

33454

American (AMR)

AF:

0.376

AC:

16784

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

9749

AN:

26106

East Asian (EAS)

AF:

0.494

AC:

19602

AN:

39688

South Asian (SAS)

AF:

0.450

AC:

38812

AN:

86194

European-Finnish (FIN)

AF:

0.405

AC:

21604

AN:

53360

Middle Eastern (MID)

AF:

0.301

AC:

1739

AN:

5768

European-Non Finnish (NFE)

AF:

0.352

AC:

391753

AN:

1111454

Other (OTH)

AF:

0.350

AC:

21102

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

18415

36830

55244

73659

92074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12580

25160

37740

50320

62900

<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:

0.293

AC:

44582

AN:

152024

Hom.:

7939

Cov.:

AF XY:

0.300

AC XY:

22298

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0890

AC:

3694

AN:

41498

American (AMR)

AF:

0.344

AC:

5251

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1276

AN:

3472

East Asian (EAS)

AF:

0.515

AC:

2654

AN:

5150

South Asian (SAS)

AF:

0.445

AC:

2141

AN:

4814

European-Finnish (FIN)

AF:

0.418

AC:

4418

AN:

10570

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24144

AN:

67938

Other (OTH)

AF:

0.289

AC:

609

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1463

2926

4388

5851

7314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.329

Hom.:

27095

Bravo

AF:

0.278

TwinsUK

AF:

0.353

AC:

1309

ALSPAC

AF:

0.364

AC:

1404

ESP6500AA

AF:

0.0906

AC:

399

ESP6500EA

AF:

0.352

AC:

3030

ExAC

AF:

0.360

AC:

43655

Asia WGS

AF:

0.396

AC:

1376

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.9

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0049

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.20

MetaRNN

Benign

0.000047

MetaSVM

Benign

-0.93

PhyloP100

0.60

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.76

REVEL

Benign

0.045

Sift

Benign

0.19

Sift4G

Benign

0.51

Polyphen

0.057

Vest4

0.038

MPC

0.032

ClinPred

0.0029

GERP RS

1.2

Varity_R

0.087

gMVP

0.22

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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