8-6876346-T-C

Position:

• chr8-6876346-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.61+1451A>G 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 151,914 control chromosomes in the GnomAD database, including 51,627 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 0.82 (51627 hom., cov: 31)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.50

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=-1.04).
• 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	Protein	UniProt
DEFB1	NM_005218.4	c.61+1451A>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.61+1451A>G		intron_variant		1	NM_005218.4	ENSP00000297439.3
GS1-24F4.2	ENST00000531701.1	n.226-8776T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 124875 AN: 151796 Hom.: 51586 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.823 AC: 124981 AN: 151914 Hom.: 51627 Cov.: 31 AF XY: 0.822 AC XY: 61012 AN XY: 74240

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.835

Alfa AF: 0.768 Hom.: 2649

Bravo AF: 0.824

Asia WGS AF: 0.830 AC: 2884 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.046
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs5743437; hg19: chr8-6733868;