Genetic Variant MAN1C1:c.1257+87G>A (chr1-25771859-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020379.4(MAN1C1):c.1257+87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 984,606 control chromosomes in the GnomAD database, including 16,553 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 0.21 ( 3810 hom., cov: 33)

Exomes 𝑓: 0.17 ( 12743 hom. )

Consequence

MAN1C1
NM_020379.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.484

Publications

10 publications found

Variant links:

Genes affected

MAN1C1 (HGNC:19080): (mannosidase alpha class 1C member 1) Predicted to enable mannosyl-oligosaccharide 1,2-alpha-mannosidase activity. Predicted to be involved in N-glycan processing. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MAN1C1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MAN1C1	NM_020379.4	MANE Select	c.1257+87G>A	intron	N/A	NP_065112.1
MAN1C1	NM_001385182.1		c.1359+87G>A	intron	N/A	NP_001372111.1
MAN1C1	NM_001385183.1		c.1329+87G>A	intron	N/A	NP_001372112.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MAN1C1	ENST00000374332.9	TSL:1 MANE Select	c.1257+87G>A	intron	N/A	ENSP00000363452.4
MAN1C1	ENST00000263979.7	TSL:5	c.717+87G>A	intron	N/A	ENSP00000263979.3
MAN1C1	ENST00000374329.1	TSL:2	c.570+87G>A	intron	N/A	ENSP00000363449.1

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31992

AN:

152058

Hom.:

3805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.197

GnomAD4 exome

AF:

0.174

AC:

144637

AN:

832430

Hom.:

12743

Cov.:

AF XY:

0.169

AC XY:

73664

AN XY:

435162

show subpopulations

African (AFR)

AF:

0.318

AC:

6595

AN:

20720

American (AMR)

AF:

0.283

AC:

11075

AN:

39202

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

3640

AN:

20060

East Asian (EAS)

AF:

0.226

AC:

7999

AN:

35410

South Asian (SAS)

AF:

0.128

AC:

8612

AN:

67408

European-Finnish (FIN)

AF:

0.161

AC:

7687

AN:

47710

Middle Eastern (MID)

AF:

0.136

AC:

508

AN:

3740

European-Non Finnish (NFE)

AF:

0.164

AC:

91439

AN:

558926

Other (OTH)

AF:

0.180

AC:

7082

AN:

39254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

5840

11680

17521

23361

29201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2470

4940

7410

9880

12350

<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:

0.210

AC:

32024

AN:

152176

Hom.:

3810

Cov.:

AF XY:

0.210

AC XY:

15591

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.307

AC:

12745

AN:

41496

American (AMR)

AF:

0.257

AC:

3934

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3470

East Asian (EAS)

AF:

0.224

AC:

1157

AN:

5174

South Asian (SAS)

AF:

0.127

AC:

614

AN:

4820

European-Finnish (FIN)

AF:

0.155

AC:

1646

AN:

10596

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10660

AN:

68012

Other (OTH)

AF:

0.201

AC:

424

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1225

2450

3674

4899

6124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.179

Hom.:

2111

Bravo

AF:

0.225

Asia WGS

AF:

0.220

AC:

767

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over