8-6925931-C-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001926.4(DEFA6):c.105G>C(p.Glu35Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00335 in 1,614,016 control chromosomes in the GnomAD database, including 148 homozygotes. 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 Benign (★).
Frequency
Genomes: 𝑓 0.018 ( 63 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 85 hom. )
Consequence
DEFA6
NM_001926.4 missense
NM_001926.4 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: -0.936
Genes affected
DEFA6 (HGNC:2765): (defensin alpha 6) Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. Several alpha defensin genes appear to be clustered on chromosome 8. The protein encoded by this gene, defensin, alpha 6, is highly expressed in the secretory granules of Paneth cells of the small intestine, and likely plays a role in host defense of human bowel. [provided by RefSeq, Oct 2014]
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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=0.0026606321).
BP6
?
Variant 8-6925931-C-G is Benign according to our data. Variant chr8-6925931-C-G is described in ClinVar as [Benign]. Clinvar id is 776283.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEFA6 | NM_001926.4 | c.105G>C | p.Glu35Asp | missense_variant | 1/2 | ENST00000297436.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEFA6 | ENST00000297436.3 | c.105G>C | p.Glu35Asp | missense_variant | 1/2 | 1 | NM_001926.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0177 AC: 2688AN: 152220Hom.: 63 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00460 AC: 1154AN: 250856Hom.: 31 AF XY: 0.00348 AC XY: 472AN XY: 135600
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GnomAD4 exome AF: 0.00186 AC: 2715AN: 1461678Hom.: 85 Cov.: 31 AF XY: 0.00164 AC XY: 1191AN XY: 727128
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GnomAD4 genome ? AF: 0.0177 AC: 2698AN: 152338Hom.: 63 Cov.: 33 AF XY: 0.0170 AC XY: 1265AN XY: 74488
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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 | Jun 25, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Gain of phosphorylation at Y34 (P = 0.3515);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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