rs188075767
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000352.6(ABCC8):c.1630+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,036 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.000907 AC: 138AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000159 AC: 40AN: 251224Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135808
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1460736Hom.: 1 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 726686
GnomAD4 genome AF: 0.000900 AC: 137AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000953 AC XY: 71AN XY: 74466
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Variant summary: ABCC8 c.1630+10C>T 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. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00016 in 251224 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ABCC8 causing Congenital Hyperinsulinism (0.00016 vs 0.0034), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1630+10C>T in individuals affected with Congenital Hyperinsulinism and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (VUS, n=2; Likely benign: n=1). Based on the evidence outlined above, the variant was classified as likely benign. -
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Hereditary hyperinsulinism Uncertain:1
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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 (rs188075767) 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 (rs188075767) 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