8-6870594-T-C

Position:

• chr8-6870594-T-C

Variant summary

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

The NM_005218.4(DEFB1):​c.*87A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,531,124 control chromosomes in the GnomAD database, including 2,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (1057 hom., cov: 32)
  • Exomes 𝑓: 0.027 (1271 hom.)
• Consequence: DEFB1 NM_005218.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

Genes affected

DEFB1 (HGNC:2766): (defensin beta 1) 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 1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. This gene maps in close proximity to defensin family member, defensin, alpha 1 and has been implicated in the pathogenesis of cystic fibrosis. [provided by RefSeq, Jul 2008]

GS1-24F4.2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.*87A>G		splice_region_variant	2/2	ENST00000297439.4	NP_005209.1
DEFB1	NM_005218.4	c.*87A>G		3_prime_UTR_variant	2/2	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.*87A>G		splice_region_variant	2/2	1	NM_005218.4	ENSP00000297439.3
DEFB1	ENST00000297439	c.*87A>G		3_prime_UTR_variant	2/2	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11681 AN: 152086 Hom.: 1052 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.00980

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0669

GnomAD4 exome AF: 0.0265 AC: 36542 AN: 1378920 Hom.: 1271 Cov.: 23 AF XY: 0.0267 AC XY: 18253 AN XY: 682410

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0310

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.0386

Gnomad4 SAS exome AF: 0.0559

Gnomad4 FIN exome AF: 0.0122

Gnomad4 NFE exome AF: 0.0184

Gnomad4 OTH exome AF: 0.0344

GnomAD4 genome AF: 0.0769 AC: 11709 AN: 152204 Hom.: 1057 Cov.: 32 AF XY: 0.0754 AC XY: 5614 AN XY: 74410

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0325

Gnomad4 SAS AF: 0.0620

Gnomad4 FIN AF: 0.00980

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0358 Hom.: 271

Bravo AF: 0.0857

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1800971; hg19: chr8-6728116;