8-6873758-C-T

Position:

• chr8-6873758-C-T

Variant summary

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

The NM_005218.4(DEFB1):​c.62-2932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,778 control chromosomes in the GnomAD database, including 19,560 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 0.50 (19560 hom., cov: 31)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437

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 = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-2932G>A		intron_variant		ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-2932G>A		intron_variant		1	NM_005218.4	ENSP00000297439.3
GS1-24F4.2	ENST00000531701.1	n.226-11364C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76274 AN: 151662 Hom.: 19549 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.503 AC: 76329 AN: 151778 Hom.: 19560 Cov.: 31 AF XY: 0.505 AC XY: 37452 AN XY: 74166

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.474

Alfa AF: 0.357 Hom.: 980

Bravo AF: 0.498

Asia WGS AF: 0.410 AC: 1426 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	4.0
DANN	Benign	0.53

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: rs2741126; hg19: chr8-6731280;