8-7470469-G-C

Variant names:

• chr8-7470469-G-C
• rs746743116
• NM_001040702.1:c.106C>G

Variant summary

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

The NM_001040702.1(DEFB104B):​c.106C>G​(p.Arg36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R36C) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 2)
  • Exomes 𝑓: 0.00029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB104B NM_001040702.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 1 publications found

Genes affected

DEFB104B (HGNC:26165): (defensin beta 104B) 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 104, DEFB104A and DEFB104B, in head-to-head orientation. This gene, DEFB104B, represents the more telomeric copy. [provided by RefSeq, Oct 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.132518).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040702.1. 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
	DEFB104B	NM_001040702.1	MANE Select	c.106C>G	p.Arg36Gly	missense	Exon 2 of 2	NP_001035792.1	Q8WTQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB104B	ENST00000316169.2	TSL:1 MANE Select	c.106C>G	p.Arg36Gly	missense	Exon 2 of 2	ENSP00000322191.2	Q8WTQ1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 7 AN: 5676 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.00294

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: 0.000801

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000252 AC: 5 AN: 19824 AF XY: 0.00

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000418

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000289 AC: 53 AN: 183148 Hom.: 0 Cov.: 0 AF XY: 0.000252 AC XY: 24 AN XY: 95176

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

African (AFR) AF: 0.00325 AC: 21 AN: 6468

American (AMR) AF: 0.00 AC: 0 AN: 6482

Ashkenazi Jewish (ASJ) AF: 0.000178 AC: 1 AN: 5628

East Asian (EAS) AF: 0.00 AC: 0 AN: 10178

South Asian (SAS) AF: 0.00 AC: 0 AN: 19748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 776

European-Non Finnish (NFE) AF: 0.000245 AC: 28 AN: 114302

Other (OTH) AF: 0.000282 AC: 3 AN: 10646

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00106 AC: 6 AN: 5680 Hom.: 0 Cov.: 2 AF XY: 0.00129 AC XY: 3 AN XY: 2328

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

African (AFR) AF: 0.00233 AC: 4 AN: 1714

American (AMR) AF: 0.00 AC: 0 AN: 478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 216

East Asian (EAS) AF: 0.00 AC: 0 AN: 370

South Asian (SAS) AF: 0.00 AC: 0 AN: 232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 26

European-Non Finnish (NFE) AF: 0.000801 AC: 2 AN: 2498

Other (OTH) AF: 0.00 AC: 0 AN: 86

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000453419), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	0.092
Eigen_PC	Benign	-0.081
FATHMM_MKL	Benign	0.59	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.6
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.020	D
Vest4		0.48
MutPred		0.36		Loss of MoRF binding (P = 0.0252)
MVP		0.46
ClinPred		0.21	T
GERP RS		2.1
gMVP		0.21
Mutation Taster		=81/19	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: rs746743116; hg19: chr8-7327991;