rs302970
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NR_002174.2(CMAHP):n.204+9415C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,002 control chromosomes in the GnomAD database, including 16,759 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.39 ( 16759 hom., cov: 31)
Consequence
CMAHP
NR_002174.2 intron, non_coding_transcript
NR_002174.2 intron, non_coding_transcript
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.368
Genes affected
CMAHP (HGNC:2098): (cytidine monophospho-N-acetylneuraminic acid hydroxylase, pseudogene) Sialic acids are terminal components of the carbohydrate chains of glycoconjugates involved in ligand-receptor, cell-cell, and cell-pathogen interactions. The two most common forms of sialic acid found in mammalian cells are N-acetylneuraminic acid (Neu5Ac) and its hydroxylated derivative, N-glycolylneuraminic acid (Neu5Gc). Studies of sialic acid distribution show that Neu5Gc is not detectable in normal human tissues although it was an abundant sialic acid in other mammals. Neu5Gc is, in actuality, immunogenic in humans. The absense of Neu5Gc in humans is due to a deletion within the human gene CMAH encoding cytidine monophosphate-N-acetylneuraminic acid hydroxylase, an enzyme responsible for Neu5Gc biosynthesis. Sequences encoding the mouse, pig, and chimpanzee hydroxylase enzymes were obtained by cDNA cloning and found to be highly homologous. However, the homologous human cDNA differs from these cDNAs by a 92-bp deletion in the 5' region. This deletion, corresponding to exon 6 of the mouse hydroxylase gene, causes a frameshift mutation and premature termination of the polypeptide chain in human. It seems unlikely that the truncated human hydroxylase mRNA encodes for an active enzyme explaining why Neu5Gc is undetectable in normal human tissues. Human genomic DNA also shows evidence of this deletion which does not occur in the genomes of African great apes. Nonetheless, the CMAH gene maps to 6p21.32 in humans and great apes indicating that mutation of the CMAH gene occurred following human divergence from chimpanzees and bonobos. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CMAHP | NR_002174.2 | n.204+9415C>T | intron_variant, non_coding_transcript_variant | ||||
LOC124901282 | XR_007059515.1 | n.272+5673G>A | intron_variant, non_coding_transcript_variant | ||||
CMAHP | NR_027626.1 | n.523+9415C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CMAHP | ENST00000377993.8 | n.212+9415C>T | intron_variant, non_coding_transcript_variant | 1 | |||||
ENST00000643807.1 | n.568+9415C>T | intron_variant, non_coding_transcript_variant | |||||||
ENST00000648291.1 | n.601+5673G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.393 AC: 59621AN: 151884Hom.: 16711 Cov.: 31
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.393 AC: 59720AN: 152002Hom.: 16759 Cov.: 31 AF XY: 0.385 AC XY: 28572AN XY: 74308
GnomAD4 genome
?
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706
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3478
ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at