dbSNP rs1800971: DEFB1:c.*87A>G (chr8-6870594-T-C) – 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.*87A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,531,124 control chromosomes in the GnomAD database, including 2,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 1057 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1271 hom. )

Consequence

DEFB1
NM_005218.4 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330

Publications

13 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB1	NM_005218.4 link	c.*87A>G		splice_region_variant	Exon 2 of 2	ENST00000297439.4	NP_005209.1
DEFB1	NM_005218.4 link	c.*87A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000297439.4	NP_005209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB1	ENST00000297439.4 link	c.*87A>G		splice_region_variant	Exon 2 of 2	1	NM_005218.4	ENSP00000297439.3
DEFB1	ENST00000297439.4 link	c.*87A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_005218.4	ENSP00000297439.3

Frequencies

GnomAD3 genomes

AF:

0.0768

AC:

11681

AN:

152086

Hom.:

1052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0380

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0322

Gnomad SAS

AF:

0.0620

Gnomad FIN

AF:

0.00980

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0185

Gnomad OTH

AF:

0.0669

GnomAD4 exome

AF:

0.0265

AC:

36542

AN:

1378920

Hom.:

1271

Cov.:

AF XY:

0.0267

AC XY:

18253

AN XY:

682410

show subpopulations

African (AFR)

AF:

0.221

AC:

6892

AN:

31138

American (AMR)

AF:

0.0310

AC:

1159

AN:

37354

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

407

AN:

21988

East Asian (EAS)

AF:

0.0386

AC:

1512

AN:

39214

South Asian (SAS)

AF:

0.0559

AC:

4134

AN:

73926

European-Finnish (FIN)

AF:

0.0122

AC:

582

AN:

47822

Middle Eastern (MID)

AF:

0.0475

AC:

257

AN:

5406

European-Non Finnish (NFE)

AF:

0.0184

AC:

19629

AN:

1064832

Other (OTH)

AF:

0.0344

AC:

1970

AN:

57240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1613

3227

4840

6454

8067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

894

1788

2682

3576

4470

<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:

0.0769

AC:

11709

AN:

152204

Hom.:

1057

Cov.:

AF XY:

0.0754

AC XY:

5614

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.219

AC:

9086

AN:

41488

American (AMR)

AF:

0.0380

AC:

581

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3466

East Asian (EAS)

AF:

0.0325

AC:

168

AN:

5172

South Asian (SAS)

AF:

0.0620

AC:

299

AN:

4820

European-Finnish (FIN)

AF:

0.00980

AC:

104

AN:

10614

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0185

AC:

1260

AN:

68032

Other (OTH)

AF:

0.0662

AC:

140

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

479

959

1438

1918

2397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0428

Hom.:

582

Bravo

AF:

0.0857

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.55

PhyloP100

0.033

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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