rs6110460

chr20-227527-T-Cchr20-227527-T-G

Variant summary

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

The NM_080831.4(DEFB129):c.58+181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,984 control chromosomes in the GnomAD database, including 24,795 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 0.57 (24795 hom., cov: 31)
• Consequence: DEFB129 NM_080831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

DEFB129 (HGNC:16218): (defensin beta 129) 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB129	NM_080831.4	c.58+181T>C		intron_variant		ENST00000246105.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB129	ENST00000246105.4	c.58+181T>C		intron_variant		1	NM_080831.4	P1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85883 AN: 151862 Hom.: 24776 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.565 AC: 85944 AN: 151984 Hom.: 24795 Cov.: 31 AF XY: 0.565 AC XY: 41978 AN XY: 74284

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.491

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.512

Alfa AF: 0.520 Hom.: 20732

Bravo AF: 0.569

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.4
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6110460; hg19: chr20-208168;