8-6876251-C-T

Variant names:

• chr8-6876251-C-T
• rs5743440
• NM_005218.4:c.61+1546G>A

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+1546G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,036 control chromosomes in the GnomAD database, including 51,700 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 0.82 (51700 hom., cov: 31)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 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.61+1546G>A		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.61+1546G>A		intron	N/A	ENSP00000297439.3
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-8871C>T		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-8871C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125018 AN: 151920 Hom.: 51659 Cov.: 31

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.823 AC: 125124 AN: 152036 Hom.: 51700 Cov.: 31 AF XY: 0.822 AC XY: 61100 AN XY: 74308

African (AFR) AF: 0.889 AC: 36838 AN: 41436

American (AMR) AF: 0.764 AC: 11672 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2830 AN: 3472

East Asian (EAS) AF: 0.884 AC: 4567 AN: 5168

South Asian (SAS) AF: 0.854 AC: 4123 AN: 4826

European-Finnish (FIN) AF: 0.777 AC: 8203 AN: 10556

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54203 AN: 67992

Other (OTH) AF: 0.835 AC: 1764 AN: 2112

Alfa AF: 0.807 Hom.: 5797

Bravo AF: 0.824

Asia WGS AF: 0.826 AC: 2872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.94
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: rs5743440; hg19: chr8-6733773;