NM_001002035.2:c.88C>G

Variant names:

• chr11-71837428-C-G
• rs151229532
• NM_001002035.2:c.88C>G

Variant summary

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

The NM_001002035.2(DEFB108B):​c.88C>G​(p.Arg30Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R30H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DEFB108B NM_001002035.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

Genes affected

DEFB108B (HGNC:29966): (defensin beta 108B) 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. A pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Oct 2014]

XNDC1N-ZNF705EP-ALG1L9P (HGNC:55871): (XNDC1N-ZNF705EP-ALG1L9P readthrough) This locus represents naturally occurring readthrough transcription between the neighboring XNDC1N (XRCC1 N-terminal domain containing 1-like), ZNF705P (zinc finger protein 705, pseudogene) and ALG1L9P (ALG1 like 9, pseudogene) genes on chromosome 11q13.4. These readthrough transcripts are candidates for nonsense-mediated mRNA decay (NMD), and are unlikely to produce a protein product. [provided by RefSeq, Aug 2021]

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=0.2455911).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002035.2. 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
	DEFB108B	NM_001002035.2	MANE Select	c.88C>G	p.Arg30Gly	missense	Exon 2 of 2	NP_001002035.1	Q8NET1
	XNDC1N-ZNF705EP-ALG1L9P	NR_172893.1		n.708-10801G>C		intron	N/A
	XNDC1N-ZNF705EP-ALG1L9P	NR_172894.1		n.875-15881G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB108B	ENST00000328698.2	TSL:1 MANE Select	c.88C>G	p.Arg30Gly	missense	Exon 2 of 2	ENSP00000333234.1	Q8NET1
	XNDC1N-ZNF705EP-ALG1L9P	ENST00000696863.1		n.700-10801G>C		intron	N/A	ENSP00000512936.1	A0A8Q3WLN7
	DEFB108B	ENST00000529157.1	TSL:5	n.326C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459650 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 726128

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111788

Other (OTH) AF: 0.00 AC: 0 AN: 60202

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.029
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.075
Sift	Benign	0.030	D
Sift4G	Benign	0.20	T
Polyphen		0.94	P
Vest4		0.47
MutPred		0.35		Gain of ubiquitination at K25 (P = 0.0632)
MVP		0.099
MPC		0.68
ClinPred		0.45	T
GERP RS		1.5
Varity_R		0.35
gMVP		0.38
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs151229532; hg19: chr11-71548474;