chr8-24313443-C-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_014265.6(ADAM28):c.439C>A(p.His147Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,768 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 12 hom. )
Consequence
ADAM28
NM_014265.6 missense
NM_014265.6 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.105
Genes affected
ADAM28 (HGNC:206): (ADAM metallopeptidase domain 28) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The protein encoded by this gene is a lymphocyte-expressed ADAM protein. This gene is present in a gene cluster with other members of the ADAM family on chromosome 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.007144958).
BP6
Variant 8-24313443-C-A is Benign according to our data. Variant chr8-24313443-C-A is described in ClinVar as [Benign]. Clinvar id is 708349.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 12 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAM28 | NM_014265.6 | c.439C>A | p.His147Asn | missense_variant | 6/23 | ENST00000265769.9 | NP_055080.2 | |
ADAM7-AS1 | NR_125808.1 | n.502-12514G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAM28 | ENST00000265769.9 | c.439C>A | p.His147Asn | missense_variant | 6/23 | 1 | NM_014265.6 | ENSP00000265769 | A2 | |
ADAM7-AS1 | ENST00000519689.1 | n.607-12514G>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00195 AC: 296AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00203 AC: 509AN: 250966Hom.: 4 AF XY: 0.00207 AC XY: 281AN XY: 135630
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GnomAD4 exome AF: 0.00231 AC: 3375AN: 1461498Hom.: 12 Cov.: 30 AF XY: 0.00226 AC XY: 1643AN XY: 727048
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GnomAD4 genome AF: 0.00194 AC: 296AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.00206 AC XY: 153AN XY: 74432
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Apr 17, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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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