rs2744768

Variant names:

• chr1-25730818-T-G
• rs2744768
• NM_020379.4:c.638-15850T>G

Variant summary

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

The NM_020379.4(MAN1C1):​c.638-15850T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,106 control chromosomes in the GnomAD database, including 7,250 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 0.23 (7250 hom., cov: 32)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.638-15850T>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.638-15850T>G		intron_variant	Intron 2 of 11	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000263979.7	c.98-15850T>G		intron_variant	Intron 3 of 12	5		ENSP00000263979.3
MAN1C1	ENST00000374329.1	c.-50-15850T>G		intron_variant	Intron 1 of 10	2		ENSP00000363449.1
MAN1C1	ENST00000473891.1	n.36-15850T>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35558 AN: 151988 Hom.: 7216 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.234 AC: 35652 AN: 152106 Hom.: 7250 Cov.: 32 AF XY: 0.233 AC XY: 17341 AN XY: 74362

African (AFR) AF: 0.547 AC: 22648 AN: 41428

American (AMR) AF: 0.236 AC: 3601 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.180 AC: 933 AN: 5182

South Asian (SAS) AF: 0.119 AC: 573 AN: 4812

European-Finnish (FIN) AF: 0.0939 AC: 996 AN: 10604

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5958 AN: 68006

Other (OTH) AF: 0.217 AC: 459 AN: 2114

Alfa AF: 0.130 Hom.: 3767

Bravo AF: 0.259

Asia WGS AF: 0.220 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.47
DANN	Benign	0.38
PhyloP100		-1.1
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: rs2744768; hg19: chr1-26057309; COSMIC: COSV56043421;