chr8-6873024-T-C

Position:

• chr8-6873024-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.62-2198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,234 control chromosomes in the GnomAD database, including 5,053 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 0.23 (5053 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-2198A>G		intron_variant		ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-2198A>G		intron_variant		1	NM_005218.4	ENSP00000297439.3
GS1-24F4.2	ENST00000531701.1	n.226-12098T>C		intron_variant		3
GS1-24F4.2	ENST00000655804.1	n.323-157T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35279 AN: 152116 Hom.: 5049 Cov.: 33

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.232 AC: 35286 AN: 152234 Hom.: 5053 Cov.: 33 AF XY: 0.230 AC XY: 17119 AN XY: 74422

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.279

Alfa AF: 0.190 Hom.: 578

Bravo AF: 0.232

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.62

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: rs2977779; hg19: chr8-6730546;