Variant 8-6936059-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001925.3(DEFA4):c.255T>C(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: 𝑓 0.43 ( 14663 hom., cov: 33)

Exomes 𝑓: 0.39 ( 115783 hom. )

Consequence

DEFA4
NM_001925.3 synonymous

Scores

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]

DEFA4 links:

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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
DEFA4	NM_001925.3 link	c.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
DEFA4	ENST00000297435.3 link	c.255T>C	p.Gly85Gly	synonymous_variant	3/3	1	NM_001925.3	ENSP00000297435.2		P12838

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64823

AN:

151890

Hom.:

14652

Cov.:

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.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over