Genetic Variant DEFB1:c.-52G>A (chr8-6877909-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005218.4(DEFB1):c.-52G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,557,256 control chromosomes in the GnomAD database, including 106,304 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 0.41 ( 13422 hom., cov: 32)

Exomes 𝑓: 0.36 ( 92882 hom. )

Consequence

DEFB1
NM_005218.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.49

Publications

87 publications found

Variant links:

Genes affected

DEFB1 (HGNC:2766): (defensin beta 1) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. This gene maps in close proximity to defensin family member, defensin, alpha 1 and has been implicated in the pathogenesis of cystic fibrosis. [provided by RefSeq, Jul 2008]

DEFB1 links:

GS1-24F4.2 (HGNC:):

GS1-24F4.2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4 link	c.-52G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000297439.4	NP_005209.1	P60022

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4 link	c.-52G>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_005218.4	ENSP00000297439.3		P60022

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61510

AN:

151926

Hom.:

13381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.423

GnomAD2 exomes

AF:

0.362

AC:

89998

AN:

248942

AF XY:

0.363

show subpopulations

Gnomad AFR exome

AF:

0.564

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.418

Gnomad EAS exome

AF:

0.504

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.359

AC:

505046

AN:

1405212

Hom.:

92882

Cov.:

AF XY:

0.360

AC XY:

253159

AN XY:

702270

show subpopulations

African (AFR)

AF:

0.567

AC:

18379

AN:

32414

American (AMR)

AF:

0.291

AC:

12947

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

10876

AN:

25712

East Asian (EAS)

AF:

0.472

AC:

18581

AN:

39368

South Asian (SAS)

AF:

0.393

AC:

33389

AN:

85004

European-Finnish (FIN)

AF:

0.220

AC:

11719

AN:

53182

Middle Eastern (MID)

AF:

0.480

AC:

2716

AN:

5654

European-Non Finnish (NFE)

AF:

0.353

AC:

374491

AN:

1060886

Other (OTH)

AF:

0.375

AC:

21948

AN:

58498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

15493

30986

46479

61972

77465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11968

23936

35904

47872

59840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.405

AC:

61603

AN:

152044

Hom.:

13422

Cov.:

AF XY:

0.400

AC XY:

29693

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.560

AC:

23202

AN:

41452

American (AMR)

AF:

0.361

AC:

5515

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1473

AN:

3468

East Asian (EAS)

AF:

0.482

AC:

2491

AN:

5168

South Asian (SAS)

AF:

0.398

AC:

1919

AN:

4822

European-Finnish (FIN)

AF:

0.202

AC:

2141

AN:

10580

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.345

AC:

23480

AN:

67960

Other (OTH)

AF:

0.428

AC:

903

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1828

3656

5485

7313

9141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.386

Hom.:

27156

Bravo

AF:

0.424

Asia WGS

AF:

0.458

AC:

1591

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.82

(source)

DANN

Benign

0.50

PhyloP100

-2.5

PromoterAI

0.054

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over