NM_139074.4:c.54C>T

Variant names:

• chr20-158778-C-T
• rs16995668
• NM_139074.4:c.54C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_139074.4(DEFB127):​c.54C>T​(p.Thr18Thr) 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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139074.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB127	NM_139074.4	MANE Select	c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	NP_620713.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB127	ENST00000382388.4	TSL:1 MANE Select	c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	ENSP00000371825.3

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

GnomAD2 exomes AF: 0.00675 AC: 1670 AN: 247490 AF XY: 0.00647

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 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

African (AFR) AF: 0.00389 AC: 129 AN: 33188

American (AMR) AF: 0.000364 AC: 16 AN: 43922

Ashkenazi Jewish (ASJ) AF: 0.00178 AC: 46 AN: 25850

East Asian (EAS) AF: 0.0788 AC: 3124 AN: 39656

South Asian (SAS) AF: 0.00273 AC: 234 AN: 85694

European-Finnish (FIN) AF: 0.00105 AC: 56 AN: 53232

Middle Eastern (MID) AF: 0.000873 AC: 5 AN: 5726

European-Non Finnish (NFE) AF: 0.000416 AC: 462 AN: 1110050

Other (OTH) AF: 0.00615 AC: 370 AN: 60140

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

African (AFR) AF: 0.00393 AC: 163 AN: 41500

American (AMR) AF: 0.000524 AC: 8 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.0727 AC: 377 AN: 5184

South Asian (SAS) AF: 0.00312 AC: 15 AN: 4812

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67996

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00173 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.64
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16995668; hg19: chr20-139419; COSMIC: COSV66688639;