20-144480-C-T

Position:

• chr20-144480-C-T

Variant summary

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

The NM_030931.4(DEFB126):​c.59-935C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,672 control chromosomes in the GnomAD database, including 9,487 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 0.35 (9487 hom., cov: 32)
• Consequence: DEFB126 NM_030931.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

Genes affected

DEFB126 (HGNC:15900): (defensin beta 126) 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. The encoded protein is highly similar to an epididymal-specific secretory protein (ESP13.2) from cynomolgus monkey. Mutation of this gene is associated with impaired sperm function. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB126	NM_030931.4	c.59-935C>T		intron_variant		ENST00000382398.4	NP_112193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB126	ENST00000382398.4	c.59-935C>T		intron_variant		1	NM_030931.4	ENSP00000371835	P1
DEFB126	ENST00000542572.1	n.54-935C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52412 AN: 151554 Hom.: 9489 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.346 AC: 52429 AN: 151672 Hom.: 9487 Cov.: 32 AF XY: 0.346 AC XY: 25658 AN XY: 74062

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.349

Alfa AF: 0.390 Hom.: 16002

Bravo AF: 0.342

Asia WGS AF: 0.245 AC: 853 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1342137; hg19: chr20-125121;