rs9356970

Variant names:

• chr6-25257738-G-A
• rs9356970
• ENST00000413898.2:n.518-2432C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-25257738-G-A
• chr6-25257738-G-C
• chr6-25257738-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000413898.2(CMAHP):​n.518-2432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,202 control chromosomes in the GnomAD database, including 7,886 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 0.29 (7886 hom., cov: 33)
• Consequence: CMAHP ENST00000413898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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]

LOC101928663 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101928663	NR_110862.1	n.514-2432C>T		intron_variant	Intron 2 of 3
LOC101928663	NR_110863.1	n.513+2610C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMAHP	ENST00000413898.2	n.518-2432C>T		intron_variant	Intron 2 of 3	1
CMAHP	ENST00000643481.1	n.517-2432C>T		intron_variant	Intron 2 of 5
CMAHP	ENST00000643656.2	n.267-2432C>T		intron_variant	Intron 2 of 4
CMAHP	ENST00000643807.1	n.364+112208C>T		intron_variant	Intron 3 of 15

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43473 AN: 152086 Hom.: 7882 Cov.: 33

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43477 AN: 152202 Hom.: 7886 Cov.: 33 AF XY: 0.298 AC XY: 22158 AN XY: 74412

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.264

Alfa AF: 0.308 Hom.: 7518

Bravo AF: 0.262

Asia WGS AF: 0.467 AC: 1622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9356970; hg19: chr6-25257966;