rs148698681
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_015295.3(SMCHD1):c.5878+12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,517,278 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
SMCHD1
NM_015295.3 intron
NM_015295.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.36
Genes affected
SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 18-2796119-C-G is Benign according to our data. Variant chr18-2796119-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00131 (199/152236) while in subpopulation AFR AF= 0.00467 (194/41552). AF 95% confidence interval is 0.00413. There are 2 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 197 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.5878+12C>G | intron_variant | ENST00000320876.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMCHD1 | ENST00000320876.11 | c.5878+12C>G | intron_variant | 5 | NM_015295.3 | P2 | |||
ENST00000583546.1 | n.370+12336G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00130 AC: 197AN: 152118Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000525 AC: 65AN: 123888Hom.: 2 AF XY: 0.000382 AC XY: 25AN XY: 65382
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GnomAD4 exome AF: 0.000116 AC: 158AN: 1365042Hom.: 0 Cov.: 28 AF XY: 0.0000906 AC XY: 61AN XY: 673478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Facioscapulohumeral muscular dystrophy 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at