8-6873024-T-C

Variant names:

• chr8-6873024-T-C
• rs2977779
• NM_005218.4:c.62-2198A>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.62-2198A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,234 control chromosomes in the GnomAD database, including 5,053 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 0.23 (5053 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005218.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB1	NM_005218.4	MANE Select	c.62-2198A>G		intron	N/A	NP_005209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB1	ENST00000297439.4	TSL:1 MANE Select	c.62-2198A>G		intron	N/A	ENSP00000297439.3
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-12098T>C		intron	N/A
	GS1-24F4.2	ENST00000655804.2		n.340-157T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35279 AN: 152116 Hom.: 5049 Cov.: 33

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.232 AC: 35286 AN: 152234 Hom.: 5053 Cov.: 33 AF XY: 0.230 AC XY: 17119 AN XY: 74422

African (AFR) AF: 0.0694 AC: 2883 AN: 41562

American (AMR) AF: 0.274 AC: 4195 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2281 AN: 5170

South Asian (SAS) AF: 0.265 AC: 1279 AN: 4822

European-Finnish (FIN) AF: 0.188 AC: 1989 AN: 10592

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20656 AN: 68004

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.242 Hom.: 1686

Bravo AF: 0.232

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.62
PhyloP100		1.0
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: rs2977779; hg19: chr8-6730546;