chr1-25714023-T-G

Variant names:

• chr1-25714023-T-G
• rs2744761
• NM_020379.4:c.637+27487T>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.637+27487T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,190 control chromosomes in the GnomAD database, including 5,019 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 (5019 hom., cov: 32)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 3 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=-0.39).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1C1	NM_020379.4	MANE Select	c.637+27487T>G		intron	N/A	NP_065112.1	Q9NR34
	MAN1C1	NM_001385182.1		c.638-26047T>G		intron	N/A	NP_001372111.1
	MAN1C1	NM_001385183.1		c.637+27487T>G		intron	N/A	NP_001372112.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1C1	ENST00000374332.9	TSL:1 MANE Select	c.637+27487T>G		intron	N/A	ENSP00000363452.4	Q9NR34
	MAN1C1	ENST00000899084.1		c.637+27487T>G		intron	N/A	ENSP00000569143.1
	MAN1C1	ENST00000929760.1		c.637+27487T>G		intron	N/A	ENSP00000599819.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32278 AN: 152072 Hom.: 5001 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.212 AC: 32338 AN: 152190 Hom.: 5019 Cov.: 32 AF XY: 0.211 AC XY: 15671 AN XY: 74420

African (AFR) AF: 0.436 AC: 18081 AN: 41474

American (AMR) AF: 0.232 AC: 3549 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3472

East Asian (EAS) AF: 0.179 AC: 926 AN: 5184

South Asian (SAS) AF: 0.0996 AC: 481 AN: 4828

European-Finnish (FIN) AF: 0.0960 AC: 1018 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7349 AN: 68022

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.131 Hom.: 2041

Bravo AF: 0.233

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.8
DANN	Benign	0.62
PhyloP100		-0.41
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: rs2744761; hg19: chr1-26040514;