Genetic Variant NM_021010.3:c.*109A>G (chr8-7055322-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_021010.3(DEFA5):c.*109A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 804,122 control chromosomes in the GnomAD database, including 5,722 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 ( 758 hom., cov: 33)

Exomes 𝑓: 0.12 ( 4964 hom. )

Consequence

DEFA5
NM_021010.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.803

Publications

3 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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFA5	NM_021010.3 link	c.*109A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000330590.4	NP_066290.1	Q01523

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFA5	ENST00000330590.4 link	c.*109A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_021010.3	ENSP00000329890.2		Q01523

Frequencies

GnomAD3 genomes

AF:

0.0865

AC:

13154

AN:

152124

Hom.:

759

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0689

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.0750

GnomAD4 exome

AF:

0.117

AC:

75979

AN:

651880

Hom.:

4964

Cov.:

AF XY:

0.117

AC XY:

39511

AN XY:

338918

show subpopulations

African (AFR)

AF:

0.0236

AC:

391

AN:

16580

American (AMR)

AF:

0.0571

AC:

1440

AN:

25216

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

2203

AN:

17758

East Asian (EAS)

AF:

0.000219

AC:

AN:

31892

South Asian (SAS)

AF:

0.113

AC:

6329

AN:

56032

European-Finnish (FIN)

AF:

0.128

AC:

5009

AN:

39096

Middle Eastern (MID)

AF:

0.0978

AC:

402

AN:

4110

European-Non Finnish (NFE)

AF:

0.132

AC:

56671

AN:

428422

Other (OTH)

AF:

0.108

AC:

3527

AN:

32774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

3192

6384

9576

12768

15960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1160

2320

3480

4640

5800

<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:

0.0864

AC:

13147

AN:

152242

Hom.:

758

Cov.:

AF XY:

0.0866

AC XY:

6448

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0224

AC:

929

AN:

41544

American (AMR)

AF:

0.0686

AC:

1050

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

397

AN:

3468

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.105

AC:

505

AN:

4828

European-Finnish (FIN)

AF:

0.131

AC:

1385

AN:

10588

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.127

AC:

8619

AN:

68006

Other (OTH)

AF:

0.0752

AC:

159

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

614

1229

1843

2458

3072

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:

0.110

Hom.:

208

Bravo

AF:

0.0774

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.5

(source)

DANN

Benign

0.85

PhyloP100

0.80

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

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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