dbSNP rs12624954: DEFB127:p.Gly31Arg (chr20-158815-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.369

AC:

92241

AN:

250200

Hom.:

18242

AF XY:

0.376

AC XY:

50807

AN XY:

135230

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 SAS exome

AF:

0.449

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

Gnomad4 AFR exome

AF:

0.0746

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.496

Gnomad4 SAS exome

AF:

0.450

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.352

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.293

AC:

44609

AN:

152078

Hom.:

7953

Cov.:

AF XY:

0.300

AC XY:

22311

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0890

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.367

Gnomad4 EAS

AF:

0.520

Gnomad4 SAS

AF:

0.444

Gnomad4 FIN

AF:

0.418

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.288

Alfa

AF:

0.345

Hom.:

23048

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over