8-7415528-T-C

Variant names:

• chr8-7415528-T-C
• rs2737532
• NM_001205266.2:c.59-431A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BS2: High Homozygotes in GnomAd4 at 776 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB4B	NM_001205266.2	c.59-431A>G		intron_variant	Intron 1 of 1	ENST00000318157.3	NP_001192195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB4B	ENST00000318157.3	c.59-431A>G		intron_variant	Intron 1 of 1	1	NM_001205266.2	ENSP00000424598.1

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

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

African (AFR) AF: 0.280 AC: 10637 AN: 37972

American (AMR) AF: 0.230 AC: 3291 AN: 14300

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 542 AN: 3292

East Asian (EAS) AF: 0.207 AC: 999 AN: 4822

South Asian (SAS) AF: 0.200 AC: 896 AN: 4480

European-Finnish (FIN) AF: 0.180 AC: 1800 AN: 9990

Middle Eastern (MID) AF: 0.270 AC: 76 AN: 282

European-Non Finnish (NFE) AF: 0.173 AC: 11007 AN: 63562

Other (OTH) AF: 0.207 AC: 415 AN: 2000

⚠️ 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: 0.0846 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
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2737532; hg19: chr8-7273050; COSMIC: COSV58940621; COSMIC: COSV58940621;