8-6872441-C-G

Variant names:

• chr8-6872441-C-G
• rs2978873
• NM_005218.4:c.62-1615G>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.62-1615G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,996 control chromosomes in the GnomAD database, including 2,549 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 (2549 hom., cov: 32)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• 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=-1.02).
• 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 rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.62-1615G>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.62-1615G>C		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26757 AN: 151878 Hom.: 2555 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: 0.144

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.176 AC: 26773 AN: 151996 Hom.: 2549 Cov.: 32 AF XY: 0.177 AC XY: 13138 AN XY: 74278

African (AFR) AF: 0.110 AC: 4566 AN: 41480

American (AMR) AF: 0.236 AC: 3608 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3466

East Asian (EAS) AF: 0.116 AC: 595 AN: 5134

South Asian (SAS) AF: 0.144 AC: 696 AN: 4826

European-Finnish (FIN) AF: 0.221 AC: 2323 AN: 10534

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13729 AN: 67968

Other (OTH) AF: 0.162 AC: 342 AN: 2114

Alfa AF: 0.189 Hom.: 345

Bravo AF: 0.176

Asia WGS AF: 0.170 AC: 591 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.24
PhyloP100		-0.68
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: rs2978873; hg19: chr8-6729963;