rs2702885

Variant names:

• chr8-6870996-C-G
• rs2702885
• NM_005218.4:c.62-170G>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.62-170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,258 control chromosomes in the GnomAD database, including 41,752 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 0.74 (41752 hom., cov: 36)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-170G>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.62-170G>C		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.737 AC: 112181 AN: 152138 Hom.: 41709 Cov.: 36

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.737 AC: 112278 AN: 152258 Hom.: 41752 Cov.: 36 AF XY: 0.741 AC XY: 55138 AN XY: 74436

African (AFR) AF: 0.821 AC: 34131 AN: 41554

American (AMR) AF: 0.715 AC: 10935 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2452 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2882 AN: 5186

South Asian (SAS) AF: 0.739 AC: 3564 AN: 4822

European-Finnish (FIN) AF: 0.814 AC: 8629 AN: 10604

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47393 AN: 68002

Other (OTH) AF: 0.700 AC: 1479 AN: 2112

Alfa AF: 0.731 Hom.: 5078

Bravo AF: 0.733

Asia WGS AF: 0.633 AC: 2200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		-0.17
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: rs2702885; hg19: chr8-6728518; COSMIC: COSV107391236;