chr1-25758907-G-T

Variant names:

• chr1-25758907-G-T
• rs12130495
• NM_020379.4:c.1047+198G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020379.4(MAN1C1):​c.1047+198G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 584,942 control chromosomes in the GnomAD database, including 1,667 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 0.079 (538 hom., cov: 32)
  • Exomes 𝑓: 0.064 (1129 hom.)
• Consequence: MAN1C1 NM_020379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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 = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.1047+198G>T		intron_variant	Intron 6 of 11	ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1C1	ENST00000374332.9	c.1047+198G>T		intron_variant	Intron 6 of 11	1	NM_020379.4	ENSP00000363452.4

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12012 AN: 151934 Hom.: 539 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0784

GnomAD4 exome AF: 0.0642 AC: 27811 AN: 432890 Hom.: 1129 Cov.: 3 AF XY: 0.0613 AC XY: 14050 AN XY: 229226

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0389

Gnomad4 ASJ exome AF: 0.0800

Gnomad4 EAS exome AF: 0.0000679

Gnomad4 SAS exome AF: 0.0207

Gnomad4 FIN exome AF: 0.0651

Gnomad4 NFE exome AF: 0.0774

Gnomad4 OTH exome AF: 0.0691

GnomAD4 genome AF: 0.0791 AC: 12020 AN: 152052 Hom.: 538 Cov.: 32 AF XY: 0.0751 AC XY: 5585 AN XY: 74364

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0526

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0787

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.0159 Hom.: 7

Bravo AF: 0.0800

Asia WGS AF: 0.0190 AC: 66 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	0.55
DANN	Benign	0.55

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: rs12130495; hg19: chr1-26085398;