Variant 6-25097070-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NR_002174.2(CMAHP):n.1141G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 468,096 control chromosomes in the GnomAD database, including 1,965 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 0.10 ( 1060 hom., cov: 32)

Exomes 𝑓: 0.068 ( 905 hom. )

Consequence

CMAHP
NR_002174.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

Variant links:

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]

CMAHP links:

(HGNC:):

links:

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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=-0.5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CMAHP	NR_002174.2 linkuse as main transcript	n.1141G>C		non_coding_transcript_exon_variant	8/13

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
CMAHP	ENST00000377993.8 linkuse as main transcript	n.1149G>C	non_coding_transcript_exon_variant	9/14	1
	ENST00000643807.1 linkuse as main transcript	n.1505G>C	non_coding_transcript_exon_variant	11/16
	ENST00000648291.1 linkuse as main transcript	n.392+18359C>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15765

AN:

152086

Hom.:

1053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.0476

Gnomad FIN

AF:

0.0879

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0692

Gnomad OTH

AF:

0.0989

GnomAD3 exomes

AF:

0.0688

AC:

10279

AN:

149444

Hom.:

485

AF XY:

0.0678

AC XY:

5433

AN XY:

80184

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0397

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.0287

Gnomad SAS exome

AF:

0.0545

Gnomad FIN exome

AF:

0.0828

Gnomad NFE exome

AF:

0.0689

Gnomad OTH exome

AF:

0.0674

GnomAD4 exome

AF:

0.0677

AC:

21379

AN:

315892

Hom.:

905

Cov.:

AF XY:

0.0665

AC XY:

11878

AN XY:

178566

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0402

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.0293

Gnomad4 SAS exome

AF:

0.0531

Gnomad4 FIN exome

AF:

0.0816

Gnomad4 NFE exome

AF:

0.0677

Gnomad4 OTH exome

AF:

0.0757

GnomAD4 genome

AF:

0.104

AC:

15796

AN:

152204

Hom.:

1060

Cov.:

AF XY:

0.102

AC XY:

7572

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.0624

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.0283

Gnomad4 SAS

AF:

0.0472

Gnomad4 FIN

AF:

0.0879

Gnomad4 NFE

AF:

0.0692

Gnomad4 OTH

AF:

0.0974

Alfa

AF:

0.0640

Hom.:

121

Bravo

AF:

0.106

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.24

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over