8-7416807-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001205266.2(DEFB4B):c.21C>T(p.Leu7=) variant causes a synonymous 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 11)
  • Exomes 𝑓: 0.0027 (14 hom.)
  • Failed GnomAD Quality Control
• Consequence: DEFB4B NM_001205266.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.311

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-7416807-G-A is Benign according to our data. Variant chr8-7416807-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.311 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB4B	NM_001205266.2	c.21C>T	p.Leu7=	synonymous_variant	1/2	ENST00000318157.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB4B	ENST00000318157.3	c.21C>T	p.Leu7=	synonymous_variant	1/2	1	NM_001205266.2	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 283 AN: 91636 Hom.: 0 Cov.: 11 FAILED QC

Gnomad AFR AF: 0.000515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00620

Gnomad EAS AF: 0.000326

Gnomad SAS AF: 0.00686

Gnomad FIN AF: 0.00484

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.00722

GnomAD3 exomes AF: 0.00183 AC: 215 AN: 117440 Hom.: 5 AF XY: 0.00163 AC XY: 101 AN XY: 62018

Gnomad AFR exome AF: 0.000666

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00194

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00308

Gnomad FIN exome AF: 0.000276

Gnomad NFE exome AF: 0.00208

Gnomad OTH exome AF: 0.00332

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00268 AC: 2029 AN: 756900 Hom.: 14 Cov.: 13 AF XY: 0.00285 AC XY: 1094 AN XY: 383984

Gnomad4 AFR exome AF: 0.000566

Gnomad4 AMR exome AF: 0.00229

Gnomad4 ASJ exome AF: 0.00547

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00419

Gnomad4 FIN exome AF: 0.00285

Gnomad4 NFE exome AF: 0.00269

Gnomad4 OTH exome AF: 0.00234

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00307 AC: 282 AN: 91726 Hom.: 0 Cov.: 11 AF XY: 0.00299 AC XY: 128 AN XY: 42866

Gnomad4 AFR AF: 0.000513

Gnomad4 AMR AF: 0.00302

Gnomad4 ASJ AF: 0.00620

Gnomad4 EAS AF: 0.000327

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.00484

Gnomad4 NFE AF: 0.00415

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00385 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

DEFB4B: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.4
Dann	Benign	0.55

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: rs529912644; hg19: chr8-7274329;