NM_000352.6:c.2117-12C>A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000352.6(ABCC8):c.2117-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,608,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000352.6 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000813 AC: 20AN: 246140Hom.: 0 AF XY: 0.0000525 AC XY: 7AN XY: 133234
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1456498Hom.: 0 Cov.: 32 AF XY: 0.0000166 AC XY: 12AN XY: 724034
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74332
ClinVar
Submissions by phenotype
not specified Benign:2
Variant summary: ABCC8 c.2117-12C>A alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing (TrAP). However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.1e-05 in 246140 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ABCC8 causing Congenital Hyperinsulinism (8.1e-05 vs 0.0034), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2117-12C>A in individuals affected with Congenital Hyperinsulinism and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 35607). Based on the evidence outlined above, the variant was classified as likely benign. -
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Maturity onset diabetes mellitus in young Uncertain:1
Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs193922398) in MODY yet. -
Transitory neonatal diabetes mellitus Uncertain:1
Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs193922398) in neonatal diabetes yet. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at