rs16995668

Positions:

• chr20-158778-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_139074.4(DEFB127):​c.54C>T​(p.Thr18=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,609,612 control chromosomes in the GnomAD database, including 145 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.

• Frequency:
  • Genomes: 𝑓 0.0040 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (132 hom.)
• Consequence: DEFB127 NM_139074.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB127	NM_139074.4	c.54C>T	p.Thr18=	synonymous_variant	2/2	ENST00000382388.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB127	ENST00000382388.4	c.54C>T	p.Thr18=	synonymous_variant	2/2	1	NM_139074.4	P1

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 610 AN: 152034 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00675 AC: 1670 AN: 247490 Hom.: 58 AF XY: 0.00647 AC XY: 867 AN XY: 133946

Gnomad AFR exome AF: 0.00397

Gnomad AMR exome AF: 0.000297

Gnomad ASJ exome AF: 0.00164

Gnomad EAS exome AF: 0.0739

Gnomad SAS exome AF: 0.00262

Gnomad FIN exome AF: 0.00103

Gnomad NFE exome AF: 0.000909

Gnomad OTH exome AF: 0.00517

GnomAD4 exome AF: 0.00305 AC: 4442 AN: 1457458 Hom.: 132 Cov.: 36 AF XY: 0.00308 AC XY: 2235 AN XY: 725012

Gnomad4 AFR exome AF: 0.00389

Gnomad4 AMR exome AF: 0.000364

Gnomad4 ASJ exome AF: 0.00178

Gnomad4 EAS exome AF: 0.0788

Gnomad4 SAS exome AF: 0.00273

Gnomad4 FIN exome AF: 0.00105

Gnomad4 NFE exome AF: 0.000416

Gnomad4 OTH exome AF: 0.00615

GnomAD4 genome AF: 0.00403 AC: 613 AN: 152154 Hom.: 13 Cov.: 33 AF XY: 0.00465 AC XY: 346 AN XY: 74390

Gnomad4 AFR AF: 0.00393

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0727

Gnomad4 SAS AF: 0.00312

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00161 Hom.: 5

Bravo AF: 0.00481

Asia WGS AF: 0.0360 AC: 123 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16995668; hg19: chr20-139419; COSMIC: COSV66688639;