rs7514323

Positions:

• chr1-117460097-A-G
• chr1-117460097-A-T

Variant summary

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

The NM_006699.5(MAN1A2):​c.951-392A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 151,442 control chromosomes in the GnomAD database, including 43,289 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 0.75 (43289 hom., cov: 29)
• Consequence: MAN1A2 NM_006699.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN1A2	NM_006699.5	c.951-392A>G		intron_variant		ENST00000356554.7
MAN1A2	XM_006710302.4	c.951-392A>G		intron_variant
MAN1A2	XM_011540536.4	c.951-392A>G		intron_variant
MAN1A2	XM_017000115.2	c.950+17772A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1A2	ENST00000356554.7	c.951-392A>G		intron_variant		1	NM_006699.5	P1
MAN1A2	ENST00000449370.6	c.149-392A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114216 AN: 151332 Hom.: 43257 Cov.: 29

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.755 AC: 114300 AN: 151442 Hom.: 43289 Cov.: 29 AF XY: 0.752 AC XY: 55607 AN XY: 73966

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.765

Alfa AF: 0.766 Hom.: 6046

Bravo AF: 0.748

Asia WGS AF: 0.728 AC: 2528 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.072
DANN	Benign	0.56

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: rs7514323; hg19: chr1-118002719; COSMIC: COSV62981951;