Genetic Variant DEFB119:c.-67G>A (chr20-31390550-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_153289.4(DEFB119):c.-67G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000967 in 1,483,192 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0047 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 5 hom. )

Consequence

DEFB119
NM_153289.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.18

Publications

6 publications found

Variant links:

Genes affected

DEFB119 (HGNC:18099): (defensin beta 119) This gene encodes a member of the beta subfamily of defensins. Beta-defensins are antimicrobial peptides that protect tissues and organs from infection by a variety of microorganisms. This gene is found in a cluster with other beta-defensin genes on the long arm of chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

DEFB119 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00474 (721/152204) while in subpopulation AFR AF = 0.0164 (683/41524). AF 95% confidence interval is 0.0154. There are 8 homozygotes in GnomAd4. There are 356 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEFB119	NM_153289.4 link	c.-67G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000376321.4	NP_695021.2	Q8N690-1
DEFB119	NM_153289.4 link	c.-67G>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000376321.4	NP_695021.2	Q8N690-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB119	ENST00000376321.4 link	c.-67G>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_153289.4	ENSP00000365499.3		Q8N690-1
DEFB119	ENST00000376321.4 link	c.-67G>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_153289.4	ENSP00000365499.3		Q8N690-1

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

711

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

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:

0.00335

GnomAD4 exome

AF:

0.000536

AC:

713

AN:

1330988

Hom.:

Cov.:

AF XY:

0.000466

AC XY:

312

AN XY:

669256

show subpopulations

African (AFR)

AF:

0.0167

AC:

496

AN:

29636

American (AMR)

AF:

0.00118

AC:

AN:

38954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24564

East Asian (EAS)

AF:

0.000333

AC:

AN:

39020

South Asian (SAS)

AF:

0.000231

AC:

AN:

82388

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.000812

AC:

AN:

4928

European-Non Finnish (NFE)

AF:

0.0000419

AC:

AN:

1002796

Other (OTH)

AF:

0.00165

AC:

AN:

55764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00474

AC:

721

AN:

152204

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

356

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0164

AC:

683

AN:

41524

American (AMR)

AF:

0.00157

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68012

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.00577

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

-2.2

PromoterAI

-0.051

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over