Variant 6-50019125-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001037497.2(DEFB110):c.56C>T(p.Ala19Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,610,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

DEFB110
NM_001037497.2 missense, splice_region

Scores

Splicing: ADA: 0.05794

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

DEFB110 (HGNC:18091): (defensin beta 110) Defensins form a family of antimicrobial and cytotoxic peptides made by neutrophils. Defensins are short, processed peptide molecules that are classified by structure into three groups: alpha-defensins, beta-defensins and theta-defensins. All beta-defensin genes are densely clustered in four to five syntenic chromosomal regions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

DEFB110 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2885607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB110	NM_001037497.2 linkuse as main transcript	c.56C>T	p.Ala19Val	missense_variant, splice_region_variant	2/2	ENST00000371148.3	NP_001032586.1	Q30KQ9-1
DEFB110	NM_001037728.2 linkuse as main transcript	c.55+2756C>T		intron_variant			NP_001032817.1	Q30KQ9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEFB110	ENST00000371148.3 linkuse as main transcript	c.56C>T	p.Ala19Val	missense_variant, splice_region_variant	2/2	1	NM_001037497.2	ENSP00000360190.2		Q30KQ9-1
DEFB110	ENST00000393660.2 linkuse as main transcript	c.55+2756C>T		intron_variant		1		ENSP00000377270.2		Q30KQ9-2

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.0000646

AC:

AN:

247502

Hom.:

AF XY:

0.0000523

AC XY:

AN XY:

133772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000981

Gnomad OTH exome

AF:

0.000500

GnomAD4 exome

AF:

0.000113

AC:

165

AN:

1458358

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

725392

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000765

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000165

EpiControl

AF:

0.0000596

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.56C>T (p.A19V) alteration is located in exon 2 (coding exon 2) of the DEFB110 gene. This alteration results from a C to T substitution at nucleotide position 56, causing the alanine (A) at amino acid position 19 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.58

M_CAP

Benign

0.023

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.16

Sift

Uncertain

0.014

Sift4G

Uncertain

0.011

Polyphen

0.98

Vest4

0.46

MVP

0.11

MPC

0.0024

ClinPred

0.24

GERP RS

2.9

Varity_R

0.12

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.058

dbscSNV1_RF

Benign

0.29

SpliceAI score (max)

0.14

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