Variant rs45479905 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001926.4(DEFA6):c.79G>A(p.Asp27Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,770 control chromosomes in the GnomAD database, including 1,630 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 809 hom., cov: 33)

Exomes 𝑓: 0.0088 ( 821 hom. )

Consequence

DEFA6
NM_001926.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

Variant links:

Genes affected

DEFA6 (HGNC:2765): (defensin alpha 6) 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 appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 6, is highly expressed in the secretory granules of Paneth cells of the small intestine, and likely plays a role in host defense of human bowel. [provided by RefSeq, Oct 2014]

DEFA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012667179).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFA6	NM_001926.4 link	c.79G>A	p.Asp27Asn	missense_variant	1/2	ENST00000297436.3	NP_001917.1	Q01524

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFA6	ENST00000297436.3 link	c.79G>A	p.Asp27Asn	missense_variant	1/2	1	NM_001926.4	ENSP00000297436.2		Q01524

Frequencies

GnomAD3 genomes

AF:

0.0575

AC:

8759

AN:

152220

Hom.:

809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0211

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0480

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.0464

GnomAD3 exomes

AF:

0.0202

AC:

5048

AN:

250224

Hom.:

348

AF XY:

0.0184

AC XY:

2495

AN XY:

135264

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.00966

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0462

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.00875

AC:

12794

AN:

1461432

Hom.:

821

Cov.:

AF XY:

0.00922

AC XY:

6701

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0432

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.000693

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0577

AC:

8784

AN:

152338

Hom.:

809

Cov.:

AF XY:

0.0567

AC XY:

4227

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0480

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0103

Hom.:

195

Bravo

AF:

0.0638

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.189

AC:

831

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0241

AC:

2927

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00125

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.1

REVEL

Benign

0.069

Sift

Uncertain

0.013

Sift4G

Uncertain

0.048

Polyphen

0.0080

Vest4

0.061

MPC

0.00060

ClinPred

0.0068

GERP RS

0.56

Varity_R

0.11

gMVP

0.050

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