NM_030931.4:c.163_166delCAAA

Variant names:

• chr20-145514-GCAAA-G
• rs11467497
• NM_030931.4:c.163_166delCAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_030931.4(DEFB126):​c.163_166delCAAA​(p.Gln55GlyfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,613,660 control chromosomes in the GnomAD database, including 20,495 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2602 hom., cov: 28)
  • Exomes 𝑓: 0.15 (17893 hom.)
• Consequence: DEFB126 NM_030931.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.332
• Publications: 20 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 -10 ACMG points.

• BP6: Variant 20-145514-GCAAA-G is Benign according to our data. Variant chr20-145514-GCAAA-G is described in ClinVar as Benign. ClinVar VariationId is 402585.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB126	NM_030931.4	MANE Select	c.163_166delCAAA	p.Gln55GlyfsTer28	frameshift	Exon 2 of 2	NP_112193.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFB126	ENST00000382398.4	TSL:1 MANE Select	c.163_166delCAAA	p.Gln55GlyfsTer28	frameshift	Exon 2 of 2	ENSP00000371835.3
	DEFB126	ENST00000542572.1	TSL:3	n.127+31_127+34delCAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27075 AN: 151918 Hom.: 2594 Cov.: 28

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.146 AC: 36734 AN: 251278 AF XY: 0.148

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.0632

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.153 AC: 223011 AN: 1461624 Hom.: 17893 AF XY: 0.153 AC XY: 111356 AN XY: 727118

African (AFR) AF: 0.265 AC: 8853 AN: 33464

American (AMR) AF: 0.108 AC: 4833 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 5088 AN: 26128

East Asian (EAS) AF: 0.0729 AC: 2894 AN: 39698

South Asian (SAS) AF: 0.169 AC: 14615 AN: 86238

European-Finnish (FIN) AF: 0.109 AC: 5806 AN: 53416

Middle Eastern (MID) AF: 0.204 AC: 1176 AN: 5768

European-Non Finnish (NFE) AF: 0.153 AC: 169834 AN: 1111820

Other (OTH) AF: 0.164 AC: 9912 AN: 60384

GnomAD4 genome AF: 0.178 AC: 27102 AN: 152036 Hom.: 2602 Cov.: 28 AF XY: 0.174 AC XY: 12925 AN XY: 74330

African (AFR) AF: 0.260 AC: 10791 AN: 41452

American (AMR) AF: 0.148 AC: 2251 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.0716 AC: 371 AN: 5184

South Asian (SAS) AF: 0.180 AC: 866 AN: 4822

European-Finnish (FIN) AF: 0.107 AC: 1132 AN: 10588

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10317 AN: 67944

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.168 Hom.: 420

Bravo AF: 0.185

Asia WGS AF: 0.140 AC: 487 AN: 3478

EpiCase AF: 0.163

EpiControl AF: 0.162

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 2401/12518=19.1%

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=189/11	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: rs11467497; hg19: chr20-126155; COSMIC: COSV66694702;