rs1299330406

Variant names:

• chr8-7470474-G-A
• rs1299330406
• NM_001040702.1:c.101C>T

Variant summary

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

The NM_001040702.1(DEFB104B):​c.101C>T​(p.Thr34Ile) 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 2)
  • Exomes 𝑓: 0.0014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB104B NM_001040702.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64
• Publications: 0 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=0.11798793).

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.101C>T	p.Thr34Ile	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.101C>T	p.Thr34Ile	missense	Exon 2 of 2	ENSP00000322191.2	Q8WTQ1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 5 AN: 4968 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00246

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: 0.00137

Gnomad OTH AF: 0.0135

GnomAD2 exomes AF: 0.00108 AC: 23 AN: 21222 AF XY: 0.00123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00133

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00138 AC: 251 AN: 181282 Hom.: 0 Cov.: 0 AF XY: 0.00128 AC XY: 121 AN XY: 94256

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

African (AFR) AF: 0.000465 AC: 3 AN: 6456

American (AMR) AF: 0.00174 AC: 11 AN: 6338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5502

East Asian (EAS) AF: 0.00 AC: 0 AN: 9642

South Asian (SAS) AF: 0.000152 AC: 3 AN: 19726

European-Finnish (FIN) AF: 0.000799 AC: 7 AN: 8764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 768

European-Non Finnish (NFE) AF: 0.00182 AC: 207 AN: 113520

Other (OTH) AF: 0.00189 AC: 20 AN: 10566

⚠️ 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: 0.000805 AC: 4 AN: 4970 Hom.: 0 Cov.: 2 AF XY: 0.00146 AC XY: 3 AN XY: 2050

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

African (AFR) AF: 0.00 AC: 0 AN: 1508

American (AMR) AF: 0.00 AC: 0 AN: 406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 198

East Asian (EAS) AF: 0.00 AC: 0 AN: 332

South Asian (SAS) AF: 0.00 AC: 0 AN: 202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.00137 AC: 3 AN: 2186

Other (OTH) AF: 0.0139 AC: 1 AN: 72

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000101646), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000253 Hom.: 0

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	Pathogenic	0.60
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	0.15
Eigen_PC	Benign	-0.032
FATHMM_MKL	Benign	0.55	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.2	T
PhyloP100		2.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.091
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.53
MutPred		0.33		Loss of phosphorylation at T34 (P = 0.0342)
MVP		0.31
ClinPred		0.25	T
GERP RS		2.1
gMVP		0.054
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1299330406; hg19: chr8-7327996; COSMIC: COSV104605048;