rs722829

Positions:

• chr20-189060-G-A

Variant summary

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

The ENST00000334391.5(DEFB128):​c.49+515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,934 control chromosomes in the GnomAD database, including 16,255 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 0.46 (16255 hom., cov: 32)
• Consequence: DEFB128 ENST00000334391.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

Genes affected

DEFB128 (HGNC:18106): (defensin beta 128) 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB128	NM_001037732.3	c.49+515C>T		intron_variant		ENST00000334391.5	NP_001032821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB128	ENST00000334391.5	c.49+515C>T		intron_variant		1	NM_001037732.3	ENSP00000335382	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69967 AN: 151816 Hom.: 16229 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.461 AC: 70044 AN: 151934 Hom.: 16255 Cov.: 32 AF XY: 0.460 AC XY: 34146 AN XY: 74222

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.509

Alfa AF: 0.464 Hom.: 31730

Bravo AF: 0.465

Asia WGS AF: 0.475 AC: 1650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.90
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs722829; hg19: chr20-169701;