rs6077288

chr20-157819-A-Gchr20-157819-A-T

Variant summary

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

The NM_139074.4(DEFB127):c.49+226A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,008 control chromosomes in the GnomAD database, including 7,946 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 0.29 (7946 hom., cov: 32)
• Consequence: DEFB127 NM_139074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-1.04).
• 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/exons	MANE	UniProt
DEFB127	NM_139074.4	c.49+226A>G		intron_variant		ENST00000382388.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB127	ENST00000382388.4	c.49+226A>G		intron_variant		1	NM_139074.4	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44580 AN: 151890 Hom.: 7950 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.293 AC: 44575 AN: 152008 Hom.: 7946 Cov.: 32 AF XY: 0.300 AC XY: 22291 AN XY: 74314

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.288

Alfa AF: 0.328 Hom.: 2074

Bravo AF: 0.278

Asia WGS AF: 0.397 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.80
Dann	Benign	0.54

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: rs6077288; hg19: chr20-138460;