chr20-31389132-G-A

Variant names:

• chr20-31389132-G-A
• rs112304323
• ENST00000376315.2:c.160C>T

Variant summary

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

The NM_153289.4(DEFB119):​c.61+1291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: DEFB119 NM_153289.4 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• Publications: 2 publications found

Genes affected

DEFB119 (HGNC:18099): (defensin beta 119) This gene encodes a member of the beta subfamily of defensins. Beta-defensins are antimicrobial peptides that protect tissues and organs from infection by a variety of microorganisms. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [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=0.030185103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB119	NM_153289.4	c.61+1291C>T		intron_variant	Intron 1 of 1	ENST00000376321.4	NP_695021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB119	ENST00000376315.2	c.160C>T	p.Arg54Cys	missense_variant	Exon 2 of 2	1		ENSP00000365492.2
DEFB119	ENST00000376321.4	c.61+1291C>T		intron_variant	Intron 1 of 1	1	NM_153289.4	ENSP00000365499.3
DEFB119	ENST00000339144.3	c.61+1291C>T		intron_variant	Intron 1 of 2	1		ENSP00000345768.3
DEFB119	ENST00000492344.1	n.148-773C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152168 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000835 AC: 21 AN: 251490 AF XY: 0.0000515

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461886 Hom.: 0 Cov.: 35 AF XY: 0.0000358 AC XY: 26 AN XY: 727242

African (AFR) AF: 0.00111 AC: 37 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112012

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152286 Hom.: 0 Cov.: 31 AF XY: 0.000322 AC XY: 24 AN XY: 74454

African (AFR) AF: 0.00101 AC: 42 AN: 41566

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000154 Hom.: 0

Bravo AF: 0.000321

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.160C>T (p.R54C) alteration is located in exon 2 (coding exon 2) of the DEFB119 gene. This alteration results from a C to T substitution at nucleotide position 160, causing the arginine (R) at amino acid position 54 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	1.0
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.2
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.049
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.24	B
Vest4		0.37
MVP		0.16
MPC		0.66
ClinPred		0.24	T
GERP RS		0.82
gMVP		0.56
Mutation Taster		=100/0	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: rs112304323; hg19: chr20-29976935; COSMIC: COSV100191093;