rs45613938

chr8-6877563-C-G

Variant summary

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

The NM_005218.4(DEFB1):c.61+234G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 152,336 control chromosomes in the GnomAD database, including 72 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 0.022 (72 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.61+234G>C		intron_variant		ENST00000297439.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB1	ENST00000297439.4	c.61+234G>C		intron_variant		1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-7559C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3278 AN: 152218 Hom.: 72 Cov.: 33

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0746

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0216

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0215 AC: 3276 AN: 152336 Hom.: 72 Cov.: 33 AF XY: 0.0219 AC XY: 1628 AN XY: 74490

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0749

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.0216

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0199 Hom.: 13

Bravo AF: 0.0209

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.5
Dann	Benign	0.66

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: rs45613938; hg19: chr8-6735085;