rs2246979

Variant names:

• chr1-25738795-G-A
• rs2246979
• NM_020379.4:c.638-7873G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020379.4(MAN1C1):​c.638-7873G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,090 control chromosomes in the GnomAD database, including 9,779 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 0.26 (9779 hom., cov: 32)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1C1	NM_020379.4	MANE Select	c.638-7873G>A		intron	N/A	NP_065112.1
	MAN1C1	NM_001385182.1		c.638-1275G>A		intron	N/A	NP_001372111.1
	MAN1C1	NM_001385183.1		c.638-7873G>A		intron	N/A	NP_001372112.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1C1	ENST00000374332.9	TSL:1 MANE Select	c.638-7873G>A		intron	N/A	ENSP00000363452.4
	MAN1C1	ENST00000263979.7	TSL:5	c.98-7873G>A		intron	N/A	ENSP00000263979.3
	MAN1C1	ENST00000374329.1	TSL:2	c.-50-7873G>A		intron	N/A	ENSP00000363449.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39622 AN: 151972 Hom.: 9737 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.261 AC: 39725 AN: 152090 Hom.: 9779 Cov.: 32 AF XY: 0.258 AC XY: 19202 AN XY: 74338

African (AFR) AF: 0.647 AC: 26811 AN: 41420

American (AMR) AF: 0.240 AC: 3670 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 390 AN: 3466

East Asian (EAS) AF: 0.180 AC: 932 AN: 5176

South Asian (SAS) AF: 0.102 AC: 492 AN: 4816

European-Finnish (FIN) AF: 0.0931 AC: 987 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0866 AC: 5889 AN: 68016

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.168 Hom.: 1796

Bravo AF: 0.291

Asia WGS AF: 0.211 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.0
DANN	Benign	0.86
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2246979; hg19: chr1-26065286; COSMIC: COSV56043444;