chr20-157914-T-C

Variant names:

• chr20-157914-T-C
• rs1858594
• NM_139074.4:c.49+321T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139074.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB127	NM_139074.4	MANE Select	c.49+321T>C		intron	N/A	NP_620713.1	Q9H1M4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB127	ENST00000382388.4	TSL:1 MANE Select	c.49+321T>C		intron	N/A	ENSP00000371825.3	Q9H1M4

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

African (AFR) AF: 0.0989 AC: 3679 AN: 37200

American (AMR) AF: 0.375 AC: 5223 AN: 13926

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1273 AN: 3348

East Asian (EAS) AF: 0.533 AC: 2659 AN: 4986

South Asian (SAS) AF: 0.479 AC: 2129 AN: 4448

European-Finnish (FIN) AF: 0.448 AC: 4377 AN: 9774

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.367 AC: 24130 AN: 65802

Other (OTH) AF: 0.316 AC: 611 AN: 1936

Alfa AF: 0.326 Hom.: 3023

Bravo AF: 0.278

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.4
DANN	Benign	0.78
PhyloP100		-0.20
PromoterAI		0.0034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1858594; hg19: chr20-138555;