rs1434789

Variant names:

• chr20-157259-T-G
• rs1434789
• NM_139074.4:c.-286T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139074.4(DEFB127):​c.-286T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,052 control chromosomes in the GnomAD database, including 8,030 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 0.30 (8030 hom., cov: 31)
• Consequence: DEFB127 NM_139074.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

DEFB127 (HGNC:16206): (defensin beta 127) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The antimicrobial protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 20p13. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -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 = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB127	NM_139074.4	c.-286T>G		upstream_gene_variant		ENST00000382388.4	NP_620713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB127	ENST00000382388.4	c.-286T>G		upstream_gene_variant		1	NM_139074.4	ENSP00000371825.3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45454 AN: 151934 Hom.: 8034 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.299 AC: 45446 AN: 152052 Hom.: 8030 Cov.: 31 AF XY: 0.305 AC XY: 22665 AN XY: 74308

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.295

Alfa AF: 0.342 Hom.: 9027

Bravo AF: 0.285

Asia WGS AF: 0.399 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1434789; hg19: chr20-137900;