chr8-7894760-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_004942.4(DEFB4A):c.48G>A(p.Met16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 147,584 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.022 ( 16 hom., cov: 23)
Exomes 𝑓: 0.023 ( 188 hom. )
Failed GnomAD Quality Control
Consequence
DEFB4A
NM_004942.4 missense
NM_004942.4 missense
Scores
1
15
Clinical Significance
Conservation
PhyloP100: -0.650
Genes affected
DEFB4A (HGNC:2767): (defensin beta 4A) 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 4, an antibiotic peptide which is locally regulated by inflammation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0030982792).
BP6
Variant 8-7894760-G-A is Benign according to our data. Variant chr8-7894760-G-A is described in ClinVar as [Benign]. Clinvar id is 773220.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0218 (3223/147584) while in subpopulation NFE AF= 0.0262 (1719/65628). AF 95% confidence interval is 0.0252. There are 16 homozygotes in gnomad4. There are 1767 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 16 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEFB4A | NM_004942.4 | c.48G>A | p.Met16Ile | missense_variant | 1/2 | ENST00000302247.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEFB4A | ENST00000302247.3 | c.48G>A | p.Met16Ile | missense_variant | 1/2 | 1 | NM_004942.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0219 AC: 3223AN: 147462Hom.: 16 Cov.: 23
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GnomAD3 exomes AF: 0.0240 AC: 5871AN: 244434Hom.: 31 AF XY: 0.0247 AC XY: 3262AN XY: 132136
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0232 AC: 32682AN: 1410374Hom.: 188 Cov.: 32 AF XY: 0.0229 AC XY: 16095AN XY: 702128
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.0218 AC: 3223AN: 147584Hom.: 16 Cov.: 23 AF XY: 0.0246 AC XY: 1767AN XY: 71962
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2017 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of catalytic residue at M16 (P = 0.2319);
MPC
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at