rs4259430

Variant names:

• chr8-7474815-A-G
• rs4259430
• NM_001040702.1:c.58+196T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040702.1(DEFB104B):​c.58+196T>C variant causes a intron 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.

• Frequency:
  • Genomes: 𝑓 0.14 (1535 hom., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: DEFB104B NM_001040702.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).

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.58+196T>C		intron	N/A	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.58+196T>C		intron	N/A	ENSP00000322191.2	Q8WTQ1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 14668 AN: 108280 Hom.: 1536 Cov.: 24

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.0840

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.135 AC: 14666 AN: 108376 Hom.: 1535 Cov.: 24 AF XY: 0.139 AC XY: 7327 AN XY: 52620

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

African (AFR) AF: 0.0324 AC: 1125 AN: 34758

American (AMR) AF: 0.204 AC: 2121 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 318 AN: 2504

East Asian (EAS) AF: 0.153 AC: 543 AN: 3542

South Asian (SAS) AF: 0.156 AC: 507 AN: 3244

European-Finnish (FIN) AF: 0.288 AC: 1853 AN: 6442

Middle Eastern (MID) AF: 0.0897 AC: 21 AN: 234

European-Non Finnish (NFE) AF: 0.176 AC: 7959 AN: 45112

Other (OTH) AF: 0.122 AC: 173 AN: 1422

⚠️ 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: 0.214 Hom.: 548

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.28
PhyloP100		-1.3
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4259430;

hg19: chr8-7332337;