chr11-17406616-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000352.6(ABCC8):c.3329+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 1,611,936 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000352.6 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0127 AC: 1931AN: 152146Hom.: 12 Cov.: 32
GnomAD3 exomes AF: 0.0114 AC: 2845AN: 249098Hom.: 24 AF XY: 0.0114 AC XY: 1529AN XY: 134630
GnomAD4 exome AF: 0.0178 AC: 26049AN: 1459672Hom.: 281 Cov.: 31 AF XY: 0.0172 AC XY: 12459AN XY: 725766
GnomAD4 genome AF: 0.0127 AC: 1929AN: 152264Hom.: 12 Cov.: 32 AF XY: 0.0114 AC XY: 852AN XY: 74446
ClinVar
Submissions by phenotype
not provided Benign:5
ABCC8: BP4, BS1, BS2 -
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This variant is associated with the following publications: (PMID: 23652837) -
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not specified Benign:4
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Variant summary: ABCC8 c.3329+6C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational 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 0.012 in 274898 control chromosomes in the gnomAD database, including 26 homozygotes. The observed variant frequency is approximately 557705.035 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCC8 causing Neonatal Diabetes Mellitus phenotype (2.1e-08), strongly suggesting that the variant is benign. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. -
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Hereditary hyperinsulinism Benign:1
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Hyperinsulinemic hypoglycemia, familial, 1 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Diabetes mellitus, transient neonatal, 2 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Permanent neonatal diabetes mellitus Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Transitory neonatal diabetes mellitus Benign:1
Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may respond to sulfonylureas. However, no sufficient evidence is found to ascertain the role of rs113873225 variant in Diabetes Mellitus yet. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at