Variant 8-7894760-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004942.4(DEFB4A):c.48G>A(p.Met16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 147,584 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 16 hom., cov: 23)

Exomes 𝑓: 0.023 ( 188 hom. )

Failed GnomAD Quality Control

Consequence

DEFB4A
NM_004942.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.650

Variant links:

Genes affected

DEFB4A (HGNC:2767): (defensin beta 4A) Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. This gene encodes defensin, beta 4, an antibiotic peptide which is locally regulated by inflammation. [provided by RefSeq, Jul 2008]

DEFB4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030982792).

BP6

Variant 8-7894760-G-A is Benign according to our data. Variant chr8-7894760-G-A is described in ClinVar as [Benign]. Clinvar id is 773220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0218 (3223/147584) while in subpopulation NFE AF= 0.0262 (1719/65628). AF 95% confidence interval is 0.0252. There are 16 homozygotes in gnomad4. There are 1767 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEFB4A	NM_004942.4 linkuse as main transcript	c.48G>A	p.Met16Ile	missense_variant	1/2	ENST00000302247.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEFB4A	ENST00000302247.3 linkuse as main transcript	c.48G>A	p.Met16Ile	missense_variant	1/2	1	NM_004942.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3223

AN:

147462

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0134

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0178

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00612

Gnomad FIN

AF:

0.0946

Gnomad MID

AF:

0.0238

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0272

GnomAD3 exomes

AF:

0.0240

AC:

5871

AN:

244434

Hom.:

AF XY:

0.0247

AC XY:

3262

AN XY:

132136

show subpopulations

Gnomad AFR exome

AF:

0.00371

Gnomad AMR exome

AF:

0.0120

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00883

Gnomad FIN exome

AF:

0.0893

Gnomad NFE exome

AF:

0.0271

Gnomad OTH exome

AF:

0.0254

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0232

AC:

32682

AN:

1410374

Hom.:

188

Cov.:

AF XY:

0.0229

AC XY:

16095

AN XY:

702128

show subpopulations

Gnomad4 AFR exome

AF:

0.00364

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0207

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00783

Gnomad4 FIN exome

AF:

0.0807

Gnomad4 NFE exome

AF:

0.0239

Gnomad4 OTH exome

AF:

0.0213

GnomAD4 genome

AF:

0.0218

AC:

3223

AN:

147584

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

1767

AN XY:

71962

show subpopulations

Gnomad4 AFR

AF:

0.00430

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0178

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00634

Gnomad4 FIN

AF:

0.0946

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.0269

Alfa

AF:

0.0332

Hom.:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0193

AC:

166

ExAC

AF:

0.0347

AC:

4214

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.65

DANN

Benign

0.81

DEOGEN2

Benign

0.042

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0044

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.52

REVEL

Benign

0.012

Sift

Benign

0.23

Sift4G

Benign

0.34

Polyphen

0.032

Vest4

0.044

MutPred

0.26

Gain of catalytic residue at M16 (P = 0.2319);

MPC

1.3

ClinPred

0.0011

GERP RS

-1.6

Varity_R

0.068

gMVP

0.037

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over