8-6873478-C-G

Variant names:

• chr8-6873478-C-G
• rs2978871
• NM_005218.4:c.62-2652G>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.62-2652G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,230 control chromosomes in the GnomAD database, including 2,453 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 0.17 (2453 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB1	NM_005218.4	MANE Select	c.62-2652G>C		intron	N/A	NP_005209.1	P60022

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB1	ENST00000297439.4	TSL:1 MANE Select	c.62-2652G>C		intron	N/A	ENSP00000297439.3	P60022
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-11644C>G		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-11644C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25517 AN: 152112 Hom.: 2459 Cov.: 33

Gnomad AFR AF: 0.0795

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.168 AC: 25525 AN: 152230 Hom.: 2453 Cov.: 33 AF XY: 0.169 AC XY: 12557 AN XY: 74408

African (AFR) AF: 0.0793 AC: 3297 AN: 41574

American (AMR) AF: 0.233 AC: 3558 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3472

East Asian (EAS) AF: 0.119 AC: 619 AN: 5186

South Asian (SAS) AF: 0.144 AC: 696 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2346 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13752 AN: 67996

Other (OTH) AF: 0.158 AC: 334 AN: 2108

Alfa AF: 0.0926 Hom.: 142

Bravo AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.30
PhyloP100		0.98
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2978871;

hg19: chr8-6731000;