rs2744772

Positions:

• chr1-25736165-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• 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/exons	MANE	UniProt
MAN1C1	NM_020379.4	c.638-10503G>A		intron_variant		ENST00000374332.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1C1	ENST00000374332.9	c.638-10503G>A		intron_variant		1	NM_020379.4	P1
MAN1C1	ENST00000263979.7	c.98-10503G>A		intron_variant		5
MAN1C1	ENST00000374329.1	c.-50-10503G>A		intron_variant		2
MAN1C1	ENST00000473891.1	n.36-10503G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0933

Gnomad4 NFE AF: 0.0867

Gnomad4 OTH AF: 0.225

Alfa AF: 0.149 Hom.: 1953

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

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: rs2744772; hg19: chr1-26062656; COSMIC: COSV56043432;