rs4259430

Positions:

• chr8-7474815-A-G

Variant summary

Our verdict is Likely benign. Variant got -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

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

Verdict is Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB104B	NM_001040702.1	c.58+196T>C		intron_variant		ENST00000316169.2	NP_001035792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB104B	ENST00000316169.2	c.58+196T>C		intron_variant		1	NM_001040702.1	ENSP00000322191.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14668 AN: 108280 Hom.: 1536 Cov.: 24 FAILED QC

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

Gnomad4 AFR AF: 0.0324

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.122

Alfa AF: 0.214 Hom.: 548

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs4259430; hg19: chr8-7332337;