rs916171
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_001388492.1(HTT):c.6953-22C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,574,388 control chromosomes in the GnomAD database, including 141,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).
Frequency
Genomes: 𝑓 0.46 ( 16911 hom., cov: 32)
Exomes 𝑓: 0.42 ( 124727 hom. )
Consequence
HTT
NM_001388492.1 intron
NM_001388492.1 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.02
Genes affected
HTT (HGNC:4851): (huntingtin) Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range of trinucleotide repeats (9-35) has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues. The larger transcript is approximately 13.7 kb and is expressed predominantly in adult and fetal brain whereas the smaller transcript of approximately 10.3 kb is more widely expressed. The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. One candidate is the huntingtin-associated protein-1, highly expressed in brain, which has increased affinity for huntingtin protein with expanded polyglutamine repeats. This gene contains an upstream open reading frame in the 5' UTR that inhibits expression of the huntingtin gene product through translational repression. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 4-3215088-C-G is Benign according to our data. Variant chr4-3215088-C-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HTT | NM_001388492.1 | c.6953-22C>G | intron_variant | ENST00000355072.11 | |||
HTT | NM_002111.8 | c.6953-22C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTT | ENST00000355072.11 | c.6953-22C>G | intron_variant | 1 | NM_001388492.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.462 AC: 70202AN: 151882Hom.: 16878 Cov.: 32
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GnomAD3 exomes AF: 0.418 AC: 101724AN: 243544Hom.: 21890 AF XY: 0.409 AC XY: 54068AN XY: 132090
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GnomAD4 exome AF: 0.415 AC: 590542AN: 1422388Hom.: 124727 Cov.: 23 AF XY: 0.410 AC XY: 291240AN XY: 709592
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GnomAD4 genome ? AF: 0.462 AC: 70281AN: 152000Hom.: 16911 Cov.: 32 AF XY: 0.460 AC XY: 34151AN XY: 74308
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at