20-259226-C-T

Variant names:

• chr20-259226-C-T
• rs145115687
• NM_207469.3:c.208C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207469.3(DEFB132):​c.208C>T​(p.Leu70Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,612,392 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000059 (1 hom.)
• Consequence: DEFB132 NM_207469.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.611
• Publications: 1 publications found

Genes affected

DEFB132 (HGNC:33806): (defensin beta 132) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The protein encoded by this gene is secreted and is a member of the beta defensin protein family. This protein binds spermatozoa and has antimicrobial activity against E. coli. 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074810684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207469.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB132	NM_207469.3	MANE Select	c.208C>T	p.Leu70Phe	missense	Exon 2 of 2	NP_997352.1	Q7Z7B7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB132	ENST00000382376.4	TSL:1 MANE Select	c.208C>T	p.Leu70Phe	missense	Exon 2 of 2	ENSP00000371813.3	Q7Z7B7

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152062 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000954 AC: 24 AN: 251478 AF XY: 0.0000809

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000589 AC: 86 AN: 1460210 Hom.: 1 Cov.: 34 AF XY: 0.0000564 AC XY: 41 AN XY: 726438

African (AFR) AF: 0.00159 AC: 53 AN: 33436

American (AMR) AF: 0.000134 AC: 6 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110936

Other (OTH) AF: 0.000365 AC: 22 AN: 60280

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152182 Hom.: 1 Cov.: 33 AF XY: 0.000417 AC XY: 31 AN XY: 74428

African (AFR) AF: 0.00123 AC: 51 AN: 41546

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000101 Hom.: 0

Bravo AF: 0.000370

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000988 AC: 12

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.61
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.015
Sift	Benign	0.30	T
Sift4G	Benign	0.22	T
Polyphen		0.35	B
Vest4		0.033
MVP		0.061
MPC		0.042
ClinPred		0.0076	T
GERP RS		-0.27
Varity_R		0.071
gMVP		0.024
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs145115687; hg19: chr20-239867;