8-6875869-AAAG-A

Variant names:

• chr8-6875869-AAAG-A
• rs10543366
• NM_005218.4:c.61+1925_61+1927delCTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005218.4(DEFB1):​c.61+1925_61+1927delCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. 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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.61+1925_61+1927delCTT		intron_variant	Intron 1 of 1	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.61+1925_61+1927delCTT		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

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

African (AFR) AF: 0.889 AC: 36800 AN: 41406

American (AMR) AF: 0.763 AC: 11645 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2827 AN: 3468

East Asian (EAS) AF: 0.883 AC: 4554 AN: 5160

South Asian (SAS) AF: 0.855 AC: 4106 AN: 4804

European-Finnish (FIN) AF: 0.776 AC: 8178 AN: 10540

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.797 AC: 54111 AN: 67900

Other (OTH) AF: 0.834 AC: 1760 AN: 2110

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10543366; hg19: chr8-6733391;