1-25725032-A-G

Variant names:

• chr1-25725032-A-G
• rs2065970
• NM_020379.4:c.638-21636A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020379.4(MAN1C1):​c.638-21636A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,124 control chromosomes in the GnomAD database, including 5,480 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 0.22 (5480 hom., cov: 32)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.638-21636A>G		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.638-21636A>G		intron_variant	Intron 2 of 11	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000263979.7	c.98-21636A>G		intron_variant	Intron 3 of 12	5		ENSP00000263979.3
MAN1C1	ENST00000374329.1	c.-51+14887A>G		intron_variant	Intron 1 of 10	2		ENSP00000363449.1
MAN1C1	ENST00000473891.1	n.36-21636A>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33432 AN: 152006 Hom.: 5464 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.220 AC: 33492 AN: 152124 Hom.: 5480 Cov.: 32 AF XY: 0.218 AC XY: 16193 AN XY: 74384

African (AFR) AF: 0.460 AC: 19067 AN: 41418

American (AMR) AF: 0.231 AC: 3540 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3470

East Asian (EAS) AF: 0.179 AC: 927 AN: 5168

South Asian (SAS) AF: 0.108 AC: 519 AN: 4826

European-Finnish (FIN) AF: 0.0975 AC: 1034 AN: 10610

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7430 AN: 68020

Other (OTH) AF: 0.216 AC: 456 AN: 2114

Alfa AF: 0.118 Hom.: 957

Bravo AF: 0.241

Asia WGS AF: 0.208 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		2.0
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: rs2065970; hg19: chr1-26051523; COSMIC: COSV56043399;