Genetic Variant DEFA4:c.*2G>A (chr8-6936018-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_001925.3(DEFA4):c.*2G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,613,382 control chromosomes in the GnomAD database, including 362,715 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 0.67 ( 34137 hom., cov: 32)

Exomes 𝑓: 0.67 ( 328578 hom. )

Consequence

DEFA4
NM_001925.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

Publications

21 publications found

Variant links:

Genes affected

DEFA4 (HGNC:2763): (defensin alpha 4) 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 alpha defensin genes are clustered on chromosome 8. This gene differs from other genes of this family by an extra 83-base segment that is apparently the result of a recent duplication within the coding region. The protein encoded by this gene, defensin, alpha 4, is found in the neutrophils; it exhibits corticostatic activity and inhibits corticotropin stimulated corticosterone production. [provided by RefSeq, Oct 2014]

DEFA4 links:

ENSG00000295941 (HGNC:):

ENSG00000295941 links:

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new If you want to explore the variant's impact on the transcript NM_001925.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001925.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA4	NM_001925.3	MANE Select	c.*2G>A		3_prime_UTR	Exon 3 of 3	NP_001916.1	P12838

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEFA4	ENST00000297435.3	TSL:1 MANE Select	c.*2G>A		3_prime_UTR	Exon 3 of 3	ENSP00000297435.2	P12838
	ENSG00000295941	ENST00000734230.1		n.134C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.667

AC:

101253

AN:

151856

Hom.:

34119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.711

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.727

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.616

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.667

Gnomad OTH

AF:

0.685

GnomAD2 exomes

AF:

0.633

AC:

159025

AN:

251302

AF XY:

0.637

show subpopulations

Gnomad AFR exome

AF:

0.713

Gnomad AMR exome

AF:

0.479

Gnomad ASJ exome

AF:

0.714

Gnomad EAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.616

Gnomad NFE exome

AF:

0.666

Gnomad OTH exome

AF:

0.661

GnomAD4 exome

AF:

0.668

AC:

976061

AN:

1461410

Hom.:

328578

Cov.:

AF XY:

0.667

AC XY:

484698

AN XY:

726992

show subpopulations

African (AFR)

AF:

0.718

AC:

24021

AN:

33468

American (AMR)

AF:

0.493

AC:

22030

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

18761

AN:

26132

East Asian (EAS)

AF:

0.600

AC:

23820

AN:

39684

South Asian (SAS)

AF:

0.626

AC:

53969

AN:

86152

European-Finnish (FIN)

AF:

0.616

AC:

32852

AN:

53358

Middle Eastern (MID)

AF:

0.692

AC:

3991

AN:

5768

European-Non Finnish (NFE)

AF:

0.680

AC:

756169

AN:

1111758

Other (OTH)

AF:

0.670

AC:

40448

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

16089

32177

48266

64354

80443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19460

38920

58380

77840

97300

<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:

0.667

AC:

101322

AN:

151972

Hom.:

34137

Cov.:

AF XY:

0.660

AC XY:

49017

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.711

AC:

29468

AN:

41470

American (AMR)

AF:

0.581

AC:

8864

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.727

AC:

2520

AN:

3468

East Asian (EAS)

AF:

0.617

AC:

3188

AN:

5170

South Asian (SAS)

AF:

0.634

AC:

3037

AN:

4790

European-Finnish (FIN)

AF:

0.616

AC:

6489

AN:

10538

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.667

AC:

45340

AN:

67972

Other (OTH)

AF:

0.691

AC:

1457

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1725

3451

5176

6902

8627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.666

Hom.:

150666

Bravo

AF:

0.667

Asia WGS

AF:

0.640

AC:

2229

AN:

3478

EpiCase

AF:

0.680

EpiControl

AF:

0.678

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

(source)

DANN

Benign

0.51

PhyloP100

-1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over