rs10543366

chr8-6875869-AAAG-Achr8-6875869-AAAG-AAAGAAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005218.4(DEFB1):c.61+1925_61+1927del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 151,852 control chromosomes in the GnomAD database, including 51,588 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51588 hom., cov: 0)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.637

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.61+1925_61+1927del		intron_variant		ENST00000297439.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB1	ENST00000297439.4	c.61+1925_61+1927del		intron_variant		1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-9250_226-9248del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124793 AN: 151734 Hom.: 51547 Cov.: 0

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.836

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

GnomAD4 genome AF: 0.823 AC: 124899 AN: 151852 Hom.: 51588 Cov.: 0 AF XY: 0.822 AC XY: 60986 AN XY: 74232

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.776

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.834

Alfa AF: 0.810 Hom.: 6082

Bravo AF: 0.823

Asia WGS AF: 0.826 AC: 2871 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs10543366; hg19: chr8-6733391;