rs807263

Positions:

• chr1-25771859-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.1257+87G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 984,606 control chromosomes in the GnomAD database, including 16,553 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 (3810 hom., cov: 33)
  • Exomes 𝑓: 0.17 (12743 hom.)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.1257+87G>A		intron_variant		ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1C1	ENST00000374332.9	c.1257+87G>A		intron_variant		1	NM_020379.4	ENSP00000363452	P1
MAN1C1	ENST00000263979.7	c.717+87G>A		intron_variant		5		ENSP00000263979
MAN1C1	ENST00000374329.1	c.570+87G>A		intron_variant		2		ENSP00000363449

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31992 AN: 152058 Hom.: 3805 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.174 AC: 144637 AN: 832430 Hom.: 12743 Cov.: 11 AF XY: 0.169 AC XY: 73664 AN XY: 435162

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.164

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.210 AC: 32024 AN: 152176 Hom.: 3810 Cov.: 33 AF XY: 0.210 AC XY: 15591 AN XY: 74398

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.201

Alfa AF: 0.168 Hom.: 1301

Bravo AF: 0.225

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs807263; hg19: chr1-26098350;