rs12624954

chr20-158815-G-Achr20-158815-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25

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]

ACMG classification

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/exons	MANE	UniProt
DEFB127	NM_139074.4	c.91G>A	p.Gly31Arg	missense_variant	2/2	ENST00000382388.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB127	ENST00000382388.4	c.91G>A	p.Gly31Arg	missense_variant	2/2	1	NM_139074.4	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44616 AN: 151964 Hom.: 7958 Cov.: 32

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

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.: 37 AF XY: 0.362 AC XY: 262704 AN XY: 726102

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.: 32 AF XY: 0.300 AC XY: 22311 AN XY: 74316

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	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.00081	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.15
Sift	Benign	0.043	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MutPred		0.13		Gain of solvent accessibility (P = 0.0037);
MPC		0.24
ClinPred		0.11	T
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

Other links and lift over

dbSNP: rs12624954; hg19: chr20-139456; COSMIC: COSV66688700;