8-6876349-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.61+1448T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,802 control chromosomes in the GnomAD database, including 13,597 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 0.42 (13597 hom., cov: 31)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB1	NM_005218.4	c.61+1448T>C		intron_variant		ENST00000297439.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB1	ENST00000297439.4	c.61+1448T>C		intron_variant		1	NM_005218.4	P1
GS1-24F4.2	ENST00000531701.1	n.226-8773A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63605 AN: 151684 Hom.: 13593 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.419 AC: 63623 AN: 151802 Hom.: 13597 Cov.: 31 AF XY: 0.424 AC XY: 31448 AN XY: 74174

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.412

Alfa AF: 0.304 Hom.: 743

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.93
Dann	Benign	0.72

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: rs2741130; hg19: chr8-6733871; COSMIC: COSV52413085;