20-158935-C-A

Variant names:

• chr20-158935-C-A
• rs16995685
• NM_139074.4:c.211C>A

Variant summary

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

The NM_139074.4(DEFB127):​c.211C>A​(p.Arg71Ser) 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 1,613,014 control chromosomes in the GnomAD database, including 104,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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 (7939 hom., cov: 32)
  • Exomes 𝑓: 0.36 (96911 hom.)
• Consequence: DEFB127 NM_139074.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

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=4.723282E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB127	NM_139074.4	c.211C>A	p.Arg71Ser	missense_variant	Exon 2 of 2	ENST00000382388.4	NP_620713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB127	ENST00000382388.4	c.211C>A	p.Arg71Ser	missense_variant	Exon 2 of 2	1	NM_139074.4	ENSP00000371825.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44587 AN: 151906 Hom.: 7944 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.443

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: 92297 AN: 250332 Hom.: 18254 AF XY: 0.376 AC XY: 50833 AN XY: 135288

Gnomad AFR exome AF: 0.0809

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.377

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.449

Gnomad FIN exome AF: 0.415

Gnomad NFE exome AF: 0.352

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.358 AC: 523641 AN: 1460990 Hom.: 96911 Cov.: 45 AF XY: 0.362 AC XY: 263005 AN XY: 726796

Gnomad4 AFR exome AF: 0.0746

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.373

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.293 AC: 44582 AN: 152024 Hom.: 7939 Cov.: 32 AF XY: 0.300 AC XY: 22298 AN XY: 74300

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.289

Alfa AF: 0.341 Hom.: 19785

Bravo AF: 0.278

TwinsUK AF: 0.353 AC: 1309

ALSPAC AF: 0.364 AC: 1404

ESP6500AA AF: 0.0906 AC: 399

ESP6500EA AF: 0.352 AC: 3030

ExAC AF: 0.360 AC: 43655

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.75
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.000047	T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.045
Sift	Benign	0.19	T
Sift4G	Benign	0.51	T
Polyphen		0.057	B
Vest4		0.038
MPC		0.032
ClinPred		0.0029	T
GERP RS		1.2
Varity_R		0.087
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs16995685; hg19: chr20-139576; COSMIC: COSV66688762;