8-6936059-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001925.3(DEFA4):ā€‹c.255T>Cā€‹(p.Gly85Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,613,472 control chromosomes in the GnomAD database, including 130,446 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: š‘“ 0.43 ( 14663 hom., cov: 33)
Exomes š‘“: 0.39 ( 115783 hom. )

Consequence

DEFA4
NM_001925.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP7
Synonymous conserved (PhyloP=-0.117 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DEFA4NM_001925.3 linkc.255T>C p.Gly85Gly synonymous_variant 3/3 ENST00000297435.3 NP_001916.1 P12838

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DEFA4ENST00000297435.3 linkc.255T>C p.Gly85Gly synonymous_variant 3/31 NM_001925.3 ENSP00000297435.2 P12838

Frequencies

GnomAD3 genomes
AF:
0.427
AC:
64823
AN:
151890
Hom.:
14652
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.553
Gnomad AMI
AF:
0.498
Gnomad AMR
AF:
0.289
Gnomad ASJ
AF:
0.347
Gnomad EAS
AF:
0.465
Gnomad SAS
AF:
0.487
Gnomad FIN
AF:
0.401
Gnomad MID
AF:
0.405
Gnomad NFE
AF:
0.382
Gnomad OTH
AF:
0.406
GnomAD3 exomes
AF:
0.389
AC:
97718
AN:
251324
Hom.:
20147
AF XY:
0.397
AC XY:
53867
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.555
Gnomad AMR exome
AF:
0.222
Gnomad ASJ exome
AF:
0.342
Gnomad EAS exome
AF:
0.464
Gnomad SAS exome
AF:
0.485
Gnomad FIN exome
AF:
0.406
Gnomad NFE exome
AF:
0.379
Gnomad OTH exome
AF:
0.374
GnomAD4 exome
AF:
0.392
AC:
573591
AN:
1461466
Hom.:
115783
Cov.:
46
AF XY:
0.395
AC XY:
286992
AN XY:
727014
show subpopulations
Gnomad4 AFR exome
AF:
0.561
Gnomad4 AMR exome
AF:
0.231
Gnomad4 ASJ exome
AF:
0.342
Gnomad4 EAS exome
AF:
0.429
Gnomad4 SAS exome
AF:
0.483
Gnomad4 FIN exome
AF:
0.404
Gnomad4 NFE exome
AF:
0.386
Gnomad4 OTH exome
AF:
0.399
GnomAD4 genome
AF:
0.427
AC:
64880
AN:
152006
Hom.:
14663
Cov.:
33
AF XY:
0.424
AC XY:
31506
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.553
Gnomad4 AMR
AF:
0.288
Gnomad4 ASJ
AF:
0.347
Gnomad4 EAS
AF:
0.466
Gnomad4 SAS
AF:
0.486
Gnomad4 FIN
AF:
0.401
Gnomad4 NFE
AF:
0.382
Gnomad4 OTH
AF:
0.410
Alfa
AF:
0.384
Hom.:
17046
Bravo
AF:
0.422
Asia WGS
AF:
0.477
AC:
1662
AN:
3478
EpiCase
AF:
0.377
EpiControl
AF:
0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.89
DANN
Benign
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2738100; hg19: chr8-6793581; COSMIC: COSV52404837; API