dbSNP rs12624954: DEFB127:p.Gly31Arg (chr20-158815-G-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.91G>A(p.Gly31Arg) 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 1,611,498 control chromosomes in the GnomAD database, including 104,884 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G31A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.29 ( 7953 hom., cov: 32)

Exomes 𝑓: 0.36 ( 96931 hom. )

Consequence

DEFB127
NM_139074.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.25

Publications

32 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=8.0904365E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB127	NM_139074.4 link	c.91G>A	p.Gly31Arg	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.91G>A	p.Gly31Arg	missense_variant	Exon 2 of 2	1	NM_139074.4	ENSP00000371825.3		Q9H1M4

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44616

AN:

151964

Hom.:

7958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0890

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.442

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:

92241

AN:

250200

AF XY:

0.376

show subpopulations

Gnomad AFR exome

AF:

0.0806

Gnomad AMR exome

AF:

0.377

Gnomad ASJ exome

AF:

0.377

Gnomad EAS exome

AF:

0.528

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.358

AC:

522978

AN:

1459420

Hom.:

96931

Cov.:

AF XY:

0.362

AC XY:

262704

AN XY:

726102

show subpopulations

African (AFR)

AF:

0.0746

AC:

2496

AN:

33448

American (AMR)

AF:

0.376

AC:

16775

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

9737

AN:

26082

East Asian (EAS)

AF:

0.496

AC:

19660

AN:

39670

South Asian (SAS)

AF:

0.450

AC:

38768

AN:

86122

European-Finnish (FIN)

AF:

0.405

AC:

21610

AN:

53376

Middle Eastern (MID)

AF:

0.302

AC:

1737

AN:

5758

European-Non Finnish (NFE)

AF:

0.352

AC:

391122

AN:

1110092

Other (OTH)

AF:

0.349

AC:

21073

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

17420

34839

52259

69678

87098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12548

25096

37644

50192

62740

<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:

44609

AN:

152078

Hom.:

7953

Cov.:

AF XY:

0.300

AC XY:

22311

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0890

AC:

3695

AN:

41534

American (AMR)

AF:

0.344

AC:

5247

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1272

AN:

3464

East Asian (EAS)

AF:

0.520

AC:

2688

AN:

5170

South Asian (SAS)

AF:

0.444

AC:

2146

AN:

4830

European-Finnish (FIN)

AF:

0.418

AC:

4409

AN:

10556

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24146

AN:

67956

Other (OTH)

AF:

0.288

AC:

609

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1463

2926

4390

5853

7316

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:

0.335

Hom.:

30187

Bravo

AF:

0.278

TwinsUK

AF:

0.353

AC:

1309

ALSPAC

AF:

0.364

AC:

1404

ESP6500AA

AF:

0.0897

AC:

395

ESP6500EA

AF:

0.352

AC:

3023

ExAC

AF:

0.360

AC:

43665

Asia WGS

AF:

0.397

AC:

1377

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.12

Eigen_PC

Benign

-0.046

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.50

MetaRNN

Benign

0.00081

MetaSVM

Benign

-0.91

PhyloP100

3.3

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-7.9

REVEL

Benign

0.15

Sift

Benign

0.043

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.30

MutPred

0.13

Gain of solvent accessibility (P = 0.0037);

MPC

0.24

ClinPred

0.11

GERP RS

3.1

Varity_R

0.54

gMVP

0.71

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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