1-117370397-A-G

Variant summary

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

The NM_006699.5(MAN1A2):c.302+1912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,058 control chromosomes in the GnomAD database, including 3,816 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 (3816 hom., cov: 32)
• Consequence: MAN1A2 NM_006699.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

MAN1A2 (HGNC:6822): (mannosidase alpha class 1A member 2) Alpha-mannosidases function at different stages of N-glycan maturation in mammalian cells. See MAN2A1 (MIM 154582) for general information.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN1A2	NM_006699.5	c.302+1912A>G		intron_variant		ENST00000356554.7
MAN1A2	XM_006710302.4	c.302+1912A>G		intron_variant
MAN1A2	XM_011540536.4	c.302+1912A>G		intron_variant
MAN1A2	XM_017000115.2	c.302+1912A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1A2	ENST00000356554.7	c.302+1912A>G		intron_variant		1	NM_006699.5	P1
MAN1A2	ENST00000482811.1	n.543+1912A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31362 AN: 151940 Hom.: 3815 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.206 AC: 31371 AN: 152058 Hom.: 3816 Cov.: 32 AF XY: 0.211 AC XY: 15652 AN XY: 74310

Gnomad4 AFR AF: 0.0844

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.214

Alfa AF: 0.226 Hom.: 1078

Bravo AF: 0.208

Asia WGS AF: 0.264 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	12
Dann	Benign	0.50

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: rs1289951; hg19: chr1-117913019; COSMIC: COSV62977019; COSMIC: COSV62977019;