dbSNP rs45628240: DEFA5:c.*166C>T (chr8-7055265-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021010.3(DEFA5):c.*166C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 581,520 control chromosomes in the GnomAD database, including 3,651 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 0.086 ( 752 hom., cov: 33)

Exomes 𝑓: 0.11 ( 2899 hom. )

Consequence

DEFA5
NM_021010.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

0 publications found

Variant links:

Genes affected

DEFA5 (HGNC:2764): (defensin alpha 5) Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several of the alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 5, is highly expressed in the secretory granules of Paneth cells of the ileum. [provided by RefSeq, Oct 2014]

DEFA5 links:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA5	NM_021010.3 link	c.*166C>T		downstream_gene_variant		ENST00000330590.4	NP_066290.1	Q01523

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA5	ENST00000330590.4 link	c.*166C>T		downstream_gene_variant		1	NM_021010.3	ENSP00000329890.2		Q01523

Frequencies

GnomAD3 genomes

AF:

0.0864

AC:

13127

AN:

151912

Hom.:

753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0223

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0686

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.0752

GnomAD4 exome

AF:

0.108

AC:

46549

AN:

429490

Hom.:

2899

Cov.:

AF XY:

0.109

AC XY:

24401

AN XY:

224454

show subpopulations

African (AFR)

AF:

0.0242

AC:

298

AN:

12294

American (AMR)

AF:

0.0602

AC:

1059

AN:

17588

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

1614

AN:

12982

East Asian (EAS)

AF:

0.000233

AC:

AN:

30054

South Asian (SAS)

AF:

0.108

AC:

4086

AN:

37940

European-Finnish (FIN)

AF:

0.128

AC:

3475

AN:

27130

Middle Eastern (MID)

AF:

0.0922

AC:

299

AN:

3242

European-Non Finnish (NFE)

AF:

0.126

AC:

33151

AN:

263294

Other (OTH)

AF:

0.103

AC:

2560

AN:

24966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1883

3766

5650

7533

9416

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

246

492

738

984

1230

<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:

0.0863

AC:

13119

AN:

152030

Hom.:

752

Cov.:

AF XY:

0.0865

AC XY:

6426

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0223

AC:

923

AN:

41474

American (AMR)

AF:

0.0684

AC:

1044

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

398

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.105

AC:

503

AN:

4812

European-Finnish (FIN)

AF:

0.131

AC:

1381

AN:

10544

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8608

AN:

67968

Other (OTH)

AF:

0.0754

AC:

159

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

620

1240

1859

2479

3099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.103

Hom.:

128

Bravo

AF:

0.0773

Asia WGS

AF:

0.0480

AC:

166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.24

(source)

DANN

Benign

0.46

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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