chr8-7415528-T-C

Position:

• chr8-7415528-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001205266.2(DEFB4B):​c.59-431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 141,572 control chromosomes in the GnomAD database, including 776 homozygotes. 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 0.21 (776 hom., cov: 35)
• Consequence: DEFB4B NM_001205266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

Genes affected

DEFB4B (HGNC:30193): (defensin beta 4B) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 4, an antibiotic peptide which is locally regulated by inflammation. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB4B	NM_001205266.2	c.59-431A>G		intron_variant		ENST00000318157.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB4B	ENST00000318157.3	c.59-431A>G		intron_variant		1	NM_001205266.2	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 29802 AN: 141462 Hom.: 775 Cov.: 35

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.211 AC: 29830 AN: 141572 Hom.: 776 Cov.: 35 AF XY: 0.211 AC XY: 14600 AN XY: 69176

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0846 Hom.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2737532; hg19: chr8-7273050; COSMIC: COSV58940621; COSMIC: COSV58940621;