Variant 6-50019035-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037497.2(DEFB110):c.146A>T(p.Asn49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DEFB110
NM_001037497.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0900

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08101717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEFB110	NM_001037497.2 linkuse as main transcript	c.146A>T	p.Asn49Ile	missense_variant	2/2	ENST00000371148.3	NP_001032586.1	Q30KQ9-1
DEFB110	NM_001037728.2 linkuse as main transcript	c.55+2846A>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.146A>T	p.Asn49Ile	missense_variant	2/2	1	NM_001037497.2	ENSP00000360190.2		Q30KQ9-1
DEFB110	ENST00000393660.2 linkuse as main transcript	c.55+2846A>T		intron_variant		1		ENSP00000377270.2		Q30KQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

250830

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461020

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

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

Jul 25, 2023

The c.146A>T (p.N49I) alteration is located in exon 2 (coding exon 2) of the DEFB110 gene. This alteration results from a A to T substitution at nucleotide position 146, causing the asparagine (N) at amino acid position 49 to be replaced by an isoleucine (I). 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

0.28

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.46

M_CAP

Benign

0.0049

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.4

REVEL

Benign

0.046

Sift

Uncertain

0.027

Sift4G

Benign

0.18

Polyphen

0.41

Vest4

0.28

MutPred

0.33

Gain of sheet (P = 0.0344);

MVP

0.11

MPC

0.0023

ClinPred

0.18

GERP RS

-4.4

Varity_R

0.23

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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