rs2737913

Positions:

• chr8-7414834-C-T

Variant summary

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

The variant allele was found at a frequency of 0.0476 in 147,436 control chromosomes in the GnomAD database, including 15 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 0.048 (15 hom., cov: 45)
  • Exomes 𝑓: 0.055 (120 hom.)
  • Failed GnomAD Quality Control
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.475

Genes affected

(HGNC:):

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.7414834C>T		intergenic_region
DEFB4B	NM_001205266.2	c.*127G>A		downstream_gene_variant		ENST00000318157.3	NP_001192195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB4B	ENST00000318157.3	c.*127G>A		downstream_gene_variant		1	NM_001205266.2	ENSP00000424598.1

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7009 AN: 147316 Hom.: 15 Cov.: 45

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.0436

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0588

Gnomad NFE AF: 0.0567

Gnomad OTH AF: 0.0543

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0549 AC: 76184 AN: 1388402 Hom.: 120 Cov.: 37 AF XY: 0.0543 AC XY: 37513 AN XY: 691026

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.0688

Gnomad4 ASJ exome AF: 0.0412

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0352

Gnomad4 NFE exome AF: 0.0555

Gnomad4 OTH exome AF: 0.0561

GnomAD4 genome AF: 0.0476 AC: 7011 AN: 147436 Hom.: 15 Cov.: 45 AF XY: 0.0488 AC XY: 3516 AN XY: 72110

Gnomad4 AFR AF: 0.0122

Gnomad4 AMR AF: 0.0876

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0567

Gnomad4 OTH AF: 0.0548

Alfa AF: 0.0593 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2737913; hg19: chr8-7272356; COSMIC: COSV58939950;