chr20-31377392-C-A

Variant names:

• chr20-31377392-C-A
• rs1184134834
• NM_153289.4:c.109G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153289.4(DEFB119):​c.109G>T​(p.Ala37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A37T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEFB119 NM_153289.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.59
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.019105524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB119	NM_153289.4	c.109G>T	p.Ala37Ser	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.109G>T	p.Ala37Ser	missense_variant	Exon 2 of 2	1	NM_153289.4	ENSP00000365499.3
DEFB119	ENST00000339144.3	c.*17G>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000345768.3
DEFB119	ENST00000492344.1	n.272G>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.0020
DANN	Benign	0.81
DEOGEN2	Benign	0.00027	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.99	T
PhyloP100		-4.6
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.014
Sift	Benign	0.98	T
Sift4G	Benign	0.55	T
Polyphen		0.0040	B
Vest4		0.14
MutPred		0.27		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.014
ClinPred		0.061	T
GERP RS		-8.2
Varity_R		0.031
Mutation Taster		=95/5	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: rs1184134834; hg19: chr20-29965195;