chr8-7470469-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001040702.1(DEFB104B):​c.106C>T​(p.Arg36Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (0 hom., cov: 2)
  • Exomes 𝑓: 0.047 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB104B NM_001040702.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028290749).
• BP6: Variant 8-7470469-G-A is Benign according to our data. Variant chr8-7470469-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2205652.Status of the report is criteria_provided_single_submitter, 1 stars.

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>T	p.Arg36Cys	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>T	p.Arg36Cys	missense	Exon 2 of 2	ENSP00000322191.2	Q8WTQ1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 137 AN: 5630 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00427

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0114

GnomAD2 exomes AF: 0.0332 AC: 659 AN: 19824 AF XY: 0.0322

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.0383

Gnomad ASJ exome AF: 0.0595

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.0833

Gnomad NFE exome AF: 0.0540

Gnomad OTH exome AF: 0.0510

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0467 AC: 8303 AN: 177734 Hom.: 2 Cov.: 0 AF XY: 0.0447 AC XY: 4134 AN XY: 92396

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

African (AFR) AF: 0.0244 AC: 156 AN: 6394

American (AMR) AF: 0.0412 AC: 260 AN: 6312

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 346 AN: 5426

East Asian (EAS) AF: 0.0000983 AC: 1 AN: 10178

South Asian (SAS) AF: 0.00708 AC: 139 AN: 19646

European-Finnish (FIN) AF: 0.0636 AC: 545 AN: 8570

Middle Eastern (MID) AF: 0.0366 AC: 28 AN: 764

European-Non Finnish (NFE) AF: 0.0570 AC: 6279 AN: 110080

Other (OTH) AF: 0.0530 AC: 549 AN: 10364

⚠️ 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: 0.0243 AC: 137 AN: 5634 Hom.: 0 Cov.: 2 AF XY: 0.0224 AC XY: 52 AN XY: 2320

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

African (AFR) AF: 0.0146 AC: 25 AN: 1714

American (AMR) AF: 0.0295 AC: 14 AN: 474

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 12 AN: 216

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

South Asian (SAS) AF: 0.00431 AC: 1 AN: 232

European-Finnish (FIN) AF: 0.0909 AC: 4 AN: 44

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

European-Non Finnish (NFE) AF: 0.0326 AC: 80 AN: 2456

Other (OTH) AF: 0.0116 AC: 1 AN: 86

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00581 AC: 15

ClinVar

ClinVar submissions

Significance: Likely benign

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Benign	0.099
Eigen_PC	Benign	-0.076
FATHMM_MKL	Benign	0.54	D
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.35
MutPred		0.36		Loss of MoRF binding (P = 0.0094)
ClinPred		0.049	T
GERP RS		2.1
gMVP		0.14
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;