rs2744772

Variant names:

• chr1-25736165-G-A
• rs2744772
• NM_020379.4:c.638-10503G>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.638-10503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,998 control chromosomes in the GnomAD database, including 9,261 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 (9261 hom., cov: 32)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.638-10503G>A		intron_variant	Intron 2 of 11	ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1C1	ENST00000374332.9	c.638-10503G>A		intron_variant	Intron 2 of 11	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000263979.7	c.98-10503G>A		intron_variant	Intron 3 of 12	5		ENSP00000263979.3
MAN1C1	ENST00000374329.1	c.-50-10503G>A		intron_variant	Intron 1 of 10	2		ENSP00000363449.1
MAN1C1	ENST00000473891.1	n.36-10503G>A		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38796 AN: 151880 Hom.: 9221 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.256 AC: 38897 AN: 151998 Hom.: 9261 Cov.: 32 AF XY: 0.253 AC XY: 18799 AN XY: 74294

African (AFR) AF: 0.629 AC: 25997 AN: 41362

American (AMR) AF: 0.238 AC: 3637 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3470

East Asian (EAS) AF: 0.177 AC: 916 AN: 5162

South Asian (SAS) AF: 0.105 AC: 504 AN: 4810

European-Finnish (FIN) AF: 0.0933 AC: 989 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0867 AC: 5897 AN: 67996

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.150 Hom.: 2181

Bravo AF: 0.285

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		0.42
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: rs2744772; hg19: chr1-26062656; COSMIC: COSV56043432;