20-144480-C-T

Variant names:

• chr20-144480-C-T
• rs1342137
• NM_030931.4:c.59-935C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030931.4. 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
	DEFB126	NM_030931.4	MANE Select	c.59-935C>T		intron	N/A	NP_112193.1	A0A384MDP8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB126	ENST00000382398.4	TSL:1 MANE Select	c.59-935C>T		intron	N/A	ENSP00000371835.3	Q9BYW3
	DEFB126	ENST00000542572.1	TSL:3	n.54-935C>T		intron	N/A

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

African (AFR) AF: 0.246 AC: 10159 AN: 41366

American (AMR) AF: 0.374 AC: 5687 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1144 AN: 5166

South Asian (SAS) AF: 0.383 AC: 1846 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4014 AN: 10500

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26709 AN: 67832

Other (OTH) AF: 0.349 AC: 734 AN: 2102

Alfa AF: 0.376 Hom.: 23195

Bravo AF: 0.342

Asia WGS AF: 0.245 AC: 853 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.49
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1342137;

hg19: chr20-125121;