8-6877165-T-C

Variant names:

• chr8-6877165-T-C
• rs2702945
• NM_005218.4:c.61+632A>G

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+632A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,166 control chromosomes in the GnomAD database, including 38,971 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 0.71 (38971 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.61+632A>G		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+632A>G		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107516 AN: 152048 Hom.: 38969 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.707 AC: 107552 AN: 152166 Hom.: 38971 Cov.: 32 AF XY: 0.709 AC XY: 52715 AN XY: 74396

African (AFR) AF: 0.535 AC: 22195 AN: 41510

American (AMR) AF: 0.708 AC: 10820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2783 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4383 AN: 5160

South Asian (SAS) AF: 0.790 AC: 3808 AN: 4822

European-Finnish (FIN) AF: 0.770 AC: 8159 AN: 10600

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52936 AN: 67998

Other (OTH) AF: 0.741 AC: 1566 AN: 2114

Alfa AF: 0.671 Hom.: 2500

Bravo AF: 0.693

Asia WGS AF: 0.760 AC: 2645 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	0.15
DANN	Benign	0.66
PhyloP100		-1.1
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: rs2702945; hg19: chr8-6734687;