20-158815-G-A

Position:

• chr20-158815-G-A

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.

• 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	Protein	UniProt
DEFB127	NM_139074.4	c.91G>A	p.Gly31Arg	missense_variant	2/2	ENST00000382388.4	NP_620713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB127	ENST00000382388.4	c.91G>A	p.Gly31Arg	missense_variant	2/2	1	NM_139074.4	ENSP00000371825	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;