Variant 8-6870777-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005218.4(DEFB1):c.111C>A(p.Cys37*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,614,210 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 3 hom. )

Consequence

DEFB1
NM_005218.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.527

Variant links:

Genes affected

DEFB1 (HGNC:2766): (defensin beta 1) 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 1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. This gene maps in close proximity to defensin family member, defensin, alpha 1 and has been implicated in the pathogenesis of cystic fibrosis. [provided by RefSeq, Jul 2008]

DEFB1 links:

GS1-24F4.2 (HGNC:):

GS1-24F4.2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 8-6870777-G-T is Benign according to our data. Variant chr8-6870777-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 712566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB1	NM_005218.4 linkuse as main transcript	c.111C>A	p.Cys37*	stop_gained	2/2	ENST00000297439.4	NP_005209.1	P60022

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DEFB1	ENST00000297439.4 linkuse as main transcript	c.111C>A	p.Cys37*	stop_gained	2/2	1	NM_005218.4	ENSP00000297439.3	P60022
GS1-24F4.2	ENST00000531701.1 linkuse as main transcript	n.226-14345G>T		intron_variant		3
GS1-24F4.2	ENST00000655804.1 linkuse as main transcript	n.323-2404G>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

345

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00794

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000656

AC:

165

AN:

251430

Hom.:

AF XY:

0.000567

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000271

AC:

396

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

161

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00944

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152328

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00789

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.0000257

Hom.:

Bravo

AF:

0.00250

ExAC

AF:

0.000725

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Benign

0.96

Eigen

Benign

-0.66

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0077

Vest4

0.76

GERP RS

-5.7

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