chr6-32029339-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_001002029.4(C4B):c.3676+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,537,142 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001002029.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C4B | NM_001002029.4 | c.3676+1G>A | splice_donor_variant | ENST00000435363.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C4B | ENST00000435363.7 | c.3676+1G>A | splice_donor_variant | 1 | NM_001002029.4 | P1 | |||
C4B | ENST00000425700.3 | c.3676+1G>A | splice_donor_variant | 1 | |||||
C4B | ENST00000647698.1 | c.2382+1G>A | splice_donor_variant | ||||||
C4B | ENST00000648821.1 | n.2289+1G>A | splice_donor_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000330 AC: 4AN: 121074Hom.: 0 Cov.: 25
GnomAD3 exomes AF: 0.00000499 AC: 1AN: 200592Hom.: 0 AF XY: 0.00000917 AC XY: 1AN XY: 109092
GnomAD4 exome AF: 0.0000113 AC: 16AN: 1416068Hom.: 1 Cov.: 33 AF XY: 0.0000114 AC XY: 8AN XY: 704208
GnomAD4 genome ? AF: 0.0000330 AC: 4AN: 121074Hom.: 0 Cov.: 25 AF XY: 0.0000342 AC XY: 2AN XY: 58564
ClinVar
Submissions by phenotype
Complement component 4b deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Breda Genetics srl | Jan 12, 2021 | Based on allele frequency, in-silico prediction scores and a certain overlap with the clinical phenotype, we interpreted this variant at least as of uncertain significance. The lack of one or more of the following features has discouraged further investigations: lack of a possible second hit in autosomal recessive conditions, presence of healthy controls in databases for autosomal dominant conditions, presence of unmatching cardinal clinical features in the patient or in the known gene-disease association, and/or variant type outside the known gene mutational spectrum. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at