rs2744768

chr1-25730818-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAN1C1	NM_020379.4	c.638-15850T>G		intron_variant		ENST00000374332.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1C1	ENST00000374332.9	c.638-15850T>G		intron_variant		1	NM_020379.4	P1
MAN1C1	ENST00000263979.7	c.98-15850T>G		intron_variant		5
MAN1C1	ENST00000374329.1	c.-50-15850T>G		intron_variant		2
MAN1C1	ENST00000473891.1	n.36-15850T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.217

Alfa AF: 0.115 Hom.: 2188

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2744768; hg19: chr1-26057309; COSMIC: COSV56043421;