chr8-6877552-C-T

Variant names:

• chr8-6877552-C-T
• rs2293959
• NM_005218.4:c.61+245G>A

Variant summary

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

The NM_005218.4(DEFB1):​c.61+245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,258 control chromosomes in the GnomAD database, including 51,073 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 (51073 hom., cov: 34)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 0 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 (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.61+245G>A		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.61+245G>A		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124333 AN: 152140 Hom.: 51032 Cov.: 34

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.817 AC: 124437 AN: 152258 Hom.: 51073 Cov.: 34 AF XY: 0.817 AC XY: 60826 AN XY: 74440

African (AFR) AF: 0.888 AC: 36903 AN: 41566

American (AMR) AF: 0.762 AC: 11666 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2815 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4598 AN: 5176

South Asian (SAS) AF: 0.850 AC: 4104 AN: 4828

European-Finnish (FIN) AF: 0.772 AC: 8187 AN: 10600

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

European-Non Finnish (NFE) AF: 0.787 AC: 53488 AN: 67992

Other (OTH) AF: 0.829 AC: 1755 AN: 2116

Alfa AF: 0.803 Hom.: 6106

Bravo AF: 0.818

Asia WGS AF: 0.826 AC: 2871 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	0.77
PhyloP100		0.20
PromoterAI		0.00020	Neutral
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: rs2293959; hg19: chr8-6735074;