rs5743480

Positions:

• chr8-6872520-A-G

Variant summary

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

The NM_005218.4(DEFB1):​c.62-1694T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 152,118 control chromosomes in the GnomAD database, including 107 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 0.028 (107 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.62-1694T>C		intron_variant		ENST00000297439.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-1694T>C		intron_variant		1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-12602A>G		intron_variant, non_coding_transcript_variant		3
GS1-24F4.2	ENST00000655804.1	n.323-661A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 4289 AN: 151996 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0214

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0325

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0282 AC: 4288 AN: 152118 Hom.: 107 Cov.: 32 AF XY: 0.0280 AC XY: 2084 AN XY: 74374

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.0325

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0277 Hom.: 14

Bravo AF: 0.0276

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.61

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: rs5743480; hg19: chr8-6730042;