6-49960419-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001037499.2(DEFB114):​c.83G>A​(p.Arg28His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000068 in 1,603,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: DEFB114 NM_001037499.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.201
• Publications: 6 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12469137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037499.2. 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
	DEFB114	NM_001037499.2	MANE Select	c.83G>A	p.Arg28His	missense	Exon 2 of 2	NP_001032588.1	Q30KQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB114	ENST00000322066.4	TSL:1 MANE Select	c.83G>A	p.Arg28His	missense	Exon 2 of 2	ENSP00000312702.3	Q30KQ6

Frequencies

GnomAD3 genomes AF: 0.0000728 AC: 11 AN: 151012 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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: 0.0000594

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000989 AC: 24 AN: 242748 AF XY: 0.0000988

Gnomad AFR exome AF: 0.000131

Gnomad AMR exome AF: 0.000211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000365

Gnomad OTH exome AF: 0.000854

GnomAD4 exome AF: 0.0000675 AC: 98 AN: 1452782 Hom.: 0 Cov.: 31 AF XY: 0.0000733 AC XY: 53 AN XY: 722790

African (AFR) AF: 0.000215 AC: 7 AN: 32552

American (AMR) AF: 0.000183 AC: 8 AN: 43744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25780

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39198

South Asian (SAS) AF: 0.0000585 AC: 5 AN: 85412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00210 AC: 12 AN: 5712

European-Non Finnish (NFE) AF: 0.0000533 AC: 59 AN: 1107302

Other (OTH) AF: 0.0000501 AC: 3 AN: 59854

GnomAD4 genome AF: 0.0000728 AC: 11 AN: 151130 Hom.: 0 Cov.: 32 AF XY: 0.0000406 AC XY: 3 AN XY: 73856

African (AFR) AF: 0.000145 AC: 6 AN: 41378

American (AMR) AF: 0.0000662 AC: 1 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000594 AC: 4 AN: 67366

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000339 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000115 AC: 14

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	0.14
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.20
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.014
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.32
MVP		0.20
MPC		0.034
ClinPred		0.054	T
GERP RS		0.75
Varity_R		0.086
gMVP		0.20
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs577162073; hg19: chr6-49928132; COSMIC: COSV59037123;