Genetic Variant CMAS:c.1114+7_1114+9dupATC (chr12-22062440-T-TATC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000229329.7(CMAS):c.1114+6_1114+7insATC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00506 in 1,611,100 control chromosomes in the GnomAD database, including 382 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 193 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 189 hom. )

Consequence

CMAS
ENST00000229329.7 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.419

Variant links:

Genes affected

CMAS (HGNC:18290): (cytidine monophosphate N-acetylneuraminic acid synthetase) This gene encodes an enzyme that converts N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc). This process is important in the formation of sialylated glycoprotein and glycolipids. This modification plays a role in cell-cell communications and immune responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CMAS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 12-22062440-T-TATC is Benign according to our data. Variant chr12-22062440-T-TATC is described in ClinVar as [Benign]. Clinvar id is 779520.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMAS	NM_018686.6 link	c.1114+7_1114+9dupATC		intron_variant	Intron 7 of 7	ENST00000229329.7	NP_061156.1	Q8NFW8-1
CMAS	NR_135117.2 link	n.1028+7_1028+9dupATC		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CMAS	ENST00000229329.7 link	c.1114+6_1114+7insATC	splice_region_variant, intron_variant	Intron 7 of 7	1	NM_018686.6	ENSP00000229329.2	Q8NFW8-1
CMAS	ENST00000534981.5 link	n.150+6_150+7insATC	splice_region_variant, intron_variant	Intron 6 of 6	1		ENSP00000446239.1	Q8NFW8-2
CMAS	ENST00000535610.5 link	n.576_577insATC	downstream_gene_variant		5		ENSP00000439404.1	F5H296
CMAS	ENST00000537658.1 link	n.27_28insATC	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4104

AN:

151744

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.00706

AC:

1753

AN:

248334

AF XY:

0.00518

show subpopulations

Gnomad AFR exome

AF:

0.0946

Gnomad AMR exome

AF:

0.00486

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000301

Gnomad OTH exome

AF:

0.00395

GnomAD4 exome

AF:

0.00277

AC:

4043

AN:

1459238

Hom.:

189

Cov.:

AF XY:

0.00235

AC XY:

1706

AN XY:

725912

show subpopulations

Gnomad4 AFR exome

AF:

0.0956

AC:

3173

AN:

33176

Gnomad4 AMR exome

AF:

0.00520

AC:

229

AN:

44062

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26064

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39652

Gnomad4 SAS exome

AF:

0.000128

AC:

AN:

85778

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53392

Gnomad4 NFE exome

AF:

0.000197

AC:

219

AN:

1111078

Gnomad4 Remaining exome

AF:

0.00642

AC:

387

AN:

60280

Heterozygous variant carriers

148

296

443

591

739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0271

AC:

4112

AN:

151862

Hom.:

193

Cov.:

AF XY:

0.0261

AC XY:

1939

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.0934

AC:

0.0934361

AN:

0.0934361

Gnomad4 AMR

AF:

0.0116

AC:

0.0116218

AN:

0.0116218

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000210

AC:

0.000209556

AN:

0.000209556

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000324

AC:

0.000323767

AN:

0.000323767

Gnomad4 OTH

AF:

0.0199

AC:

0.0199052

AN:

0.0199052

Heterozygous variant carriers

187

374

560

747

934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.0314

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism (auto)

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over