chr8-6876251-C-T

Position:

• chr8-6876251-C-T

Variant summary

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

The ENST00000297439.4(DEFB1):​c.61+1546G>A 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 152,036 control chromosomes in the GnomAD database, including 51,700 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 (51700 hom., cov: 31)
• Consequence: DEFB1 ENST00000297439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935

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=-1.0).
• 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+1546G>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.61+1546G>A		intron_variant		1	NM_005218.4	ENSP00000297439	P1
GS1-24F4.2	ENST00000531701.1	n.226-8871C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125018 AN: 151920 Hom.: 51659 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.892

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: 125124 AN: 152036 Hom.: 51700 Cov.: 31 AF XY: 0.822 AC XY: 61100 AN XY: 74308

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.835

Alfa AF: 0.807 Hom.: 5797

Bravo AF: 0.824

Asia WGS AF: 0.826 AC: 2872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.48

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: rs5743440; hg19: chr8-6733773;