20-145669-ACCC-AC

Variant names:

• chr20-145669-ACC-A
• rs11467417
• NM_030931.4:c.317_318delCC

Variant summary

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

The NM_030931.4(DEFB126):​c.317_318delCC​(p.Pro106ArgfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,611,132 control chromosomes in the GnomAD database, including 252,198 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (23238 hom., cov: 0)
  • Exomes 𝑓: 0.56 (228960 hom.)
• Consequence: DEFB126 NM_030931.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249
• Publications: 25 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 20-145669-ACC-A is Benign according to our data. Variant chr20-145669-ACC-A is described in ClinVar as Benign. ClinVar VariationId is 402586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 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.317_318delCC	p.Pro106ArgfsTer26	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.317_318delCC	p.Pro106ArgfsTer26	frameshift	Exon 2 of 2	ENSP00000371835.3
	DEFB126	ENST00000542572.1	TSL:3	n.222_223delCC		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83680 AN: 151478 Hom.: 23225 Cov.: 0

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.567

GnomAD2 exomes AF: 0.552 AC: 137216 AN: 248480 AF XY: 0.558

Gnomad AFR exome AF: 0.552

Gnomad AMR exome AF: 0.519

Gnomad ASJ exome AF: 0.685

Gnomad EAS exome AF: 0.508

Gnomad FIN exome AF: 0.493

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.559 AC: 815255 AN: 1459534 Hom.: 228960 AF XY: 0.561 AC XY: 407148 AN XY: 726052

African (AFR) AF: 0.554 AC: 18521 AN: 33456

American (AMR) AF: 0.526 AC: 23498 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 17971 AN: 26106

East Asian (EAS) AF: 0.506 AC: 20079 AN: 39684

South Asian (SAS) AF: 0.596 AC: 51328 AN: 86180

European-Finnish (FIN) AF: 0.485 AC: 25215 AN: 51948

Middle Eastern (MID) AF: 0.601 AC: 3459 AN: 5758

European-Non Finnish (NFE) AF: 0.559 AC: 620883 AN: 1111350

Other (OTH) AF: 0.568 AC: 34301 AN: 60350

GnomAD4 genome AF: 0.552 AC: 83732 AN: 151598 Hom.: 23238 Cov.: 0 AF XY: 0.549 AC XY: 40663 AN XY: 74072

African (AFR) AF: 0.552 AC: 22794 AN: 41308

American (AMR) AF: 0.546 AC: 8313 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2386 AN: 3464

East Asian (EAS) AF: 0.505 AC: 2597 AN: 5144

South Asian (SAS) AF: 0.598 AC: 2871 AN: 4802

European-Finnish (FIN) AF: 0.488 AC: 5112 AN: 10476

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37714 AN: 67884

Other (OTH) AF: 0.560 AC: 1175 AN: 2098

Alfa AF: 0.567 Hom.: 4505

Bravo AF: 0.559

Asia WGS AF: 0.491 AC: 1711 AN: 3478

EpiCase AF: 0.574

EpiControl AF: 0.571

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): 7088/12518=56.6%

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25
Mutation Taster		=195/5	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: rs11467417; hg19: chr20-126310; COSMIC: COSV66694619;