rs2293960

Positions:

• chr8-6877326-G-C
• chr8-6877326-G-T

Variant summary

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

The NM_005218.4(DEFB1):​c.61+471C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,184 control chromosomes in the GnomAD database, including 50,651 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 0.81 (50651 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.61+471C>G		intron_variant		ENST00000297439.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB1	ENST00000297439.4	c.61+471C>G		intron_variant		1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-7796G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123834 AN: 152066 Hom.: 50612 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.814 AC: 123935 AN: 152184 Hom.: 50651 Cov.: 32 AF XY: 0.814 AC XY: 60584 AN XY: 74402

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.827

Alfa AF: 0.742 Hom.: 2193

Bravo AF: 0.815

Asia WGS AF: 0.827 AC: 2875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
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: rs2293960; hg19: chr8-6734848;