8-6873080-T-G

Variant names:

• chr8-6873080-T-G
• rs2980926
• NM_005218.4:c.62-2254A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005218.4(DEFB1):​c.62-2254A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,208 control chromosomes in the GnomAD database, including 51,867 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 0.82 (51867 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-2254A>C		intron_variant	Intron 1 of 1	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.62-2254A>C		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125291 AN: 152090 Hom.: 51830 Cov.: 33

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.824 AC: 125393 AN: 152208 Hom.: 51867 Cov.: 33 AF XY: 0.823 AC XY: 61257 AN XY: 74420

African (AFR) AF: 0.891 AC: 37017 AN: 41552

American (AMR) AF: 0.763 AC: 11672 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2830 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4582 AN: 5188

South Asian (SAS) AF: 0.855 AC: 4125 AN: 4822

European-Finnish (FIN) AF: 0.779 AC: 8232 AN: 10572

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54242 AN: 67998

Other (OTH) AF: 0.839 AC: 1771 AN: 2112

Alfa AF: 0.796 Hom.: 15611

Bravo AF: 0.824

Asia WGS AF: 0.830 AC: 2887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.0
DANN	Benign	0.72
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2980926; hg19: chr8-6730602;