rs5743418

Variant names:

• chr8-6878038-G-A
• rs5743418
• ENST00000531701.2:n.602-7084G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000531701.2(GS1-24F4.2):​n.602-7084G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 590,882 control chromosomes in the GnomAD database, including 418 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 0.021 (71 hom., cov: 32)
  • Exomes 𝑓: 0.028 (347 hom.)
• Consequence: GS1-24F4.2 ENST00000531701.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 4 publications found

Genes affected

GS1-24F4.2 (HGNC:):

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]

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 = 0.0679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4	c.-181C>T		upstream_gene_variant		ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4	c.-181C>T		upstream_gene_variant		1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3212 AN: 152152 Hom.: 71 Cov.: 32

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0209

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0276 AC: 12105 AN: 438612 Hom.: 347 Cov.: 5 AF XY: 0.0311 AC XY: 7276 AN XY: 233758

African (AFR) AF: 0.0165 AC: 198 AN: 11992

American (AMR) AF: 0.0162 AC: 332 AN: 20498

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1367 AN: 12998

East Asian (EAS) AF: 0.000143 AC: 4 AN: 28058

South Asian (SAS) AF: 0.0772 AC: 3624 AN: 46972

European-Finnish (FIN) AF: 0.00462 AC: 144 AN: 31194

Middle Eastern (MID) AF: 0.0826 AC: 154 AN: 1864

European-Non Finnish (NFE) AF: 0.0212 AC: 5511 AN: 260514

Other (OTH) AF: 0.0314 AC: 771 AN: 24522

GnomAD4 genome AF: 0.0211 AC: 3210 AN: 152270 Hom.: 71 Cov.: 32 AF XY: 0.0215 AC XY: 1601 AN XY: 74448

African (AFR) AF: 0.0160 AC: 663 AN: 41558

American (AMR) AF: 0.0169 AC: 259 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4824

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0209 AC: 1420 AN: 67998

Other (OTH) AF: 0.0284 AC: 60 AN: 2116

Alfa AF: 0.0206 Hom.: 46

Bravo AF: 0.0207

Asia WGS AF: 0.0220 AC: 77 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	5.4
DANN	Benign	0.61
PhyloP100		-0.086
PromoterAI		-0.014	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5743418; hg19: chr8-6735560;