dbSNP rs807263: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4 link	c.1257+87G>A		intron_variant	Intron 8 of 11	ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MAN1C1	ENST00000374332.9 link	c.1257+87G>A	intron_variant	Intron 8 of 11	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000263979.7 link	c.717+87G>A	intron_variant	Intron 9 of 12	5		ENSP00000263979.3
MAN1C1	ENST00000374329.1 link	c.570+87G>A	intron_variant	Intron 7 of 10	2		ENSP00000363449.1
MAN1C1	ENST00000496532.5 link	n.-210G>A	upstream_gene_variant		3

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over