12-21913072-GAAA-GAA
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_020297.4(ABCC9):c.817-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,289,664 control chromosomes in the GnomAD database, including 75 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_020297.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0115 AC: 1397AN: 120982Hom.: 22 Cov.: 32
GnomAD4 exome AF: 0.0144 AC: 16825AN: 1168642Hom.: 53 Cov.: 31 AF XY: 0.0145 AC XY: 8378AN XY: 579462
GnomAD4 genome AF: 0.0115 AC: 1397AN: 121022Hom.: 22 Cov.: 32 AF XY: 0.0110 AC XY: 642AN XY: 58618
ClinVar
Submissions by phenotype
not specified Benign:6
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817-7delT in intron 5 of ABCC9: -
Variant summary: ABCC9 c.817-7delT 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 0.017 in 132398 control chromosomes in the gnomAD database, including 9 homozygotes. The observed variant frequency is approximately 660 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCC9 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.817-7delT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
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not provided Benign:3
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Dilated cardiomyopathy 1O Benign:1
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Cardiomyopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at