chr20-31377382-T-C

Variant names:

• chr20-31377382-T-C
• rs750803651
• NM_153289.4:c.119A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_153289.4(DEFB119):​c.119A>G​(p.Lys40Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: DEFB119 NM_153289.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.759
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021424055).
• BP6: Variant 20-31377382-T-C is Benign according to our data. Variant chr20-31377382-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3081313.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB119	NM_153289.4	c.119A>G	p.Lys40Arg	missense_variant	Exon 2 of 2	ENST00000376321.4	NP_695021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB119	ENST00000376321.4	c.119A>G	p.Lys40Arg	missense_variant	Exon 2 of 2	1	NM_153289.4	ENSP00000365499.3
DEFB119	ENST00000339144.3	c.*27A>G		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000345768.3
DEFB119	ENST00000492344.1	n.282A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

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: 0.00143

GnomAD2 exomes AF: 0.000151 AC: 38 AN: 251356 AF XY: 0.000147

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000417 AC: 61 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000612 AC: 16 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111968

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74308

African (AFR) AF: 0.0000242 AC: 1 AN: 41392

American (AMR) AF: 0.000196 AC: 3 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00143 AC: 3 AN: 2092

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 28, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.85
DEOGEN2	Benign	0.00097	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.76
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.029
Sift	Benign	0.20	T
Sift4G	Benign	0.36	T
Polyphen		0.0080	B
Vest4		0.13
MutPred		0.26		Loss of methylation at K40 (P = 0.0023);
MVP		0.030
ClinPred		0.013	T
GERP RS		-4.7
Varity_R		0.067
Mutation Taster		=93/7	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: rs750803651; hg19: chr20-29965185;