NM_001040704.2:c.63T>A

Variant names:

• chr8-7482739-A-T
• rs775132023
• NM_001040704.2:c.63T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040704.2(DEFB106B):​c.63T>A​(p.Phe21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 120,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: 𝑓 0.0000083 (0 hom., cov: 17)
• Consequence: DEFB106B NM_001040704.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 0 publications found

Genes affected

DEFB106B (HGNC:28879): (defensin beta 106B) 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. Chromosome 8p23 contains at least two copies of the duplicated beta-defensin cluster. This duplication results in two identical copies of defensin, beta 106, DEFB106A and DEFB106B, in head-to-head orientation. This gene, DEFB106B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1490094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040704.2. 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
	DEFB106B	NM_001040704.2	MANE Select	c.63T>A	p.Phe21Leu	missense	Exon 2 of 2	NP_001035794.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB106B	ENST00000335479.2	TSL:1 MANE Select	c.63T>A	p.Phe21Leu	missense	Exon 2 of 2	ENSP00000334364.2	Q8N104

Frequencies

GnomAD3 genomes AF: 0.00000833 AC: 1 AN: 120100 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

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: 0.0000176

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.00000833 AC: 1 AN: 120100 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 57830

African (AFR) AF: 0.00 AC: 0 AN: 31234

American (AMR) AF: 0.00 AC: 0 AN: 10696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2980

East Asian (EAS) AF: 0.00 AC: 0 AN: 3846

South Asian (SAS) AF: 0.00 AC: 0 AN: 3576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000176 AC: 1 AN: 56818

Other (OTH) AF: 0.00 AC: 0 AN: 1620

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	10
DANN	Uncertain	0.99
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.010	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.44
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Benign	0.056
Sift	Benign	0.058	T
Sift4G	Benign	0.11	T
Vest4		0.32
MutPred		0.26		Loss of stability (P = 0.0528)
MVP		0.061
ClinPred		0.19	T
GERP RS		0.22
gMVP		0.36
Mutation Taster		=96/4	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: rs775132023; hg19: chr8-7340261;