rs2977781

Positions:

• chr8-6872448-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.62-1622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,070 control chromosomes in the GnomAD database, including 2,600 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 0.18 (2600 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-1622T>C		intron_variant		ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-1622T>C		intron_variant		1	NM_005218.4	ENSP00000297439.3
GS1-24F4.2	ENST00000531701.1	n.226-12674A>G		intron_variant		3
GS1-24F4.2	ENST00000655804.1	n.323-733A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27027 AN: 151952 Hom.: 2606 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.178 AC: 27044 AN: 152070 Hom.: 2600 Cov.: 32 AF XY: 0.179 AC XY: 13328 AN XY: 74314

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.164

Alfa AF: 0.190 Hom.: 347

Bravo AF: 0.177

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.24

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: rs2977781; hg19: chr8-6729970;