NM_005218.4:c.61+2422A>G

Variant names:

• chr8-6875375-T-C
• rs5743454
• NM_005218.4:c.61+2422A>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.61+2422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 152,136 control chromosomes in the GnomAD database, including 247 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 0.044 (247 hom., cov: 33)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 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+2422A>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.61+2422A>G		intron	N/A	ENSP00000297439.3
	GS1-24F4.2	ENST00000531701.2	TSL:3	n.602-9747T>C		intron	N/A
	GS1-24F4.2	ENST00000772759.1		n.352-9747T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6755 AN: 152020 Hom.: 245 Cov.: 33

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0557

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0445 AC: 6763 AN: 152136 Hom.: 247 Cov.: 33 AF XY: 0.0482 AC XY: 3582 AN XY: 74388

African (AFR) AF: 0.0210 AC: 870 AN: 41486

American (AMR) AF: 0.0834 AC: 1274 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3468

East Asian (EAS) AF: 0.135 AC: 700 AN: 5184

South Asian (SAS) AF: 0.0922 AC: 444 AN: 4818

European-Finnish (FIN) AF: 0.0557 AC: 589 AN: 10572

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0344 AC: 2339 AN: 68010

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0396 Hom.: 310

Bravo AF: 0.0445

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.93
DANN	Benign	0.42
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

Other links and lift over

dbSNP: rs5743454; hg19: chr8-6732897;