20-157914-T-C

Position:

• chr20-157914-T-C

Variant summary

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

The NM_139074.4(DEFB127):​c.49+321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 142,594 control chromosomes in the GnomAD database, including 7,940 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 0.31 (7940 hom., cov: 31)
• Consequence: DEFB127 NM_139074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB127	NM_139074.4	c.49+321T>C		intron_variant		ENST00000382388.4	NP_620713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB127	ENST00000382388.4	c.49+321T>C		intron_variant		1	NM_139074.4	ENSP00000371825	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 44481 AN: 142474 Hom.: 7944 Cov.: 31

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.312 AC: 44477 AN: 142594 Hom.: 7940 Cov.: 31 AF XY: 0.320 AC XY: 22206 AN XY: 69286

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.316

Alfa AF: 0.319 Hom.: 1420

Bravo AF: 0.278

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.4
DANN	Benign	0.78

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: rs1858594; hg19: chr20-138555;