rs5743450

Variant names:

• chr8-6875549-T-G
• rs5743450
• NM_005218.4:c.61+2248A>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.61+2248A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 152,312 control chromosomes in the GnomAD database, including 185 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 0.042 (185 hom., cov: 34)
• Consequence: DEFB1 NM_005218.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.61+2248A>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.61+2248A>C		intron_variant	Intron 1 of 1	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6333 AN: 152194 Hom.: 185 Cov.: 34

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0831

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0501

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

GnomAD4 genome AF: 0.0416 AC: 6336 AN: 152312 Hom.: 185 Cov.: 34 AF XY: 0.0411 AC XY: 3060 AN XY: 74490

African (AFR) AF: 0.0616 AC: 2559 AN: 41538

American (AMR) AF: 0.0282 AC: 431 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0836 AC: 404 AN: 4832

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10620

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0335 AC: 2278 AN: 68040

Other (OTH) AF: 0.0496 AC: 105 AN: 2116

Alfa AF: 0.0458 Hom.: 77

Bravo AF: 0.0435

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.52
PhyloP100		0.67
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: rs5743450; hg19: chr8-6733071; COSMIC: COSV52413384;