dbSNP rs6601649: DEFB134:c.-48+900G>A (chr8-11999808-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001302695.2(DEFB134):c.-48+900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,034 control chromosomes in the GnomAD database, including 24,769 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 0.56 ( 24769 hom., cov: 32)

Consequence

DEFB134
NM_001302695.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.06

Publications

9 publications found

Variant links:

Genes affected

DEFB134 (HGNC:32399): (defensin beta 134) Defensins are cysteine-rich cationic polypeptides that are important in the immunologic response to invading microorganisms. The antimicrobial protein encoded by this gene is secreted and is a member of the beta defensin protein family. Beta defensin genes are found in several clusters throughout the genome, with this gene mapping to a cluster at 8p23. [provided by RefSeq, Nov 2014]

DEFB134 links:

OR7E160P (HGNC:31233): (olfactory receptor family 7 subfamily E member 160 pseudogene) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR7E160P links:

ENSG00000290829 (HGNC:):

ENSG00000290829 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=-1.0).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
DEFB134	NM_001302695.2 link	c.-48+900G>A	intron_variant	Intron 1 of 2	ENST00000382205.6	NP_001289624.1
OR7E160P		n.11999808C>T	intragenic_variant
DEFB134	XM_017013724.1 link	c.-48+31G>A	intron_variant	Intron 1 of 2		XP_016869213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEFB134	ENST00000382205.6 link	c.-48+900G>A		intron_variant	Intron 1 of 2	1	NM_001302695.2	ENSP00000371640.4

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84869

AN:

151916

Hom.:

24755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.724

Gnomad AMR

AF:

0.686

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.578

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.558

AC:

84907

AN:

152034

Hom.:

24769

Cov.:

AF XY:

0.572

AC XY:

42541

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.417

AC:

17278

AN:

41456

American (AMR)

AF:

0.687

AC:

10502

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1693

AN:

3468

East Asian (EAS)

AF:

0.898

AC:

4649

AN:

5176

South Asian (SAS)

AF:

0.676

AC:

3258

AN:

4818

European-Finnish (FIN)

AF:

0.681

AC:

7201

AN:

10572

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38286

AN:

67942

Other (OTH)

AF:

0.583

AC:

1229

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1845

3691

5536

7382

9227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.567

Hom.:

45600

Bravo

AF:

0.554

Asia WGS

AF:

0.736

AC:

2558

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.087

(source)

DANN

Benign

0.33

PhyloP100

-3.1

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over