chr6-49960419-C-A

Variant names:

• chr6-49960419-C-A
• rs577162073
• NM_001037499.2:c.83G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037499.2(DEFB114):​c.83G>T​(p.Arg28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 1,452,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. R28H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: DEFB114 NM_001037499.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

Genes affected

DEFB114 (HGNC:18095): (defensin beta 114) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. The protein encoded by this gene is a beta-defensin with antimicrobial activity against E. coli, S. aureus, and C. albicans. The encoded protein also binds and neutralizes lipopolysaccharide (LPS), a factor involved in inflammatory diseases and male reproductive issues. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20857182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB114	NM_001037499.2	c.83G>T	p.Arg28Leu	missense_variant	Exon 2 of 2	ENST00000322066.4	NP_001032588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB114	ENST00000322066.4	c.83G>T	p.Arg28Leu	missense_variant	Exon 2 of 2	1	NM_001037499.2	ENSP00000312702.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000742 AC: 18 AN: 242748 Hom.: 0 AF XY: 0.0000836 AC XY: 11 AN XY: 131560

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000164

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000571 AC: 83 AN: 1452782 Hom.: 0 Cov.: 31 AF XY: 0.0000540 AC XY: 39 AN XY: 722790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.0000732

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.000140 AC: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.070
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.027	D
Polyphen		0.72	P
Vest4		0.52
MutPred		0.29		Loss of MoRF binding (P = 0.0132);
MVP		0.14
MPC		0.029
ClinPred		0.20	T
GERP RS		0.75
Varity_R		0.16
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs577162073; hg19: chr6-49928132;