rs6877440

Positions:

• chr5-109708366-T-C

Variant summary

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

The NM_002372.4(MAN2A1):​c.136-5154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 151,814 control chromosomes in the GnomAD database, including 2,004 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 0.15 (2004 hom., cov: 30)
• Consequence: MAN2A1 NM_002372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

Genes affected

MAN2A1 (HGNC:6824): (mannosidase alpha class 2A member 1) This gene encodes a glycosyl hydrolase that localizes to the Golgi and catalyzes the final hydrolytic step in the asparagine-linked oligosaccharide (N-glycan) maturation pathway. Mutations in the mouse homolog of this gene have been shown to cause a systemic autoimmune disease similar to human systemic lupus erythematosus. [provided by RefSeq, Dec 2013]

MAN2A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN2A1	NM_002372.4	c.136-5154T>C		intron_variant		ENST00000261483.5	NP_002363.2
MAN2A1	XM_017009472.2	c.-12-5154T>C		intron_variant			XP_016864961.1
MAN2A1	XM_011543395.4	c.136-5154T>C		intron_variant			XP_011541697.1
MAN2A1	XR_007058604.1	n.627-5154T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN2A1	ENST00000261483.5	c.136-5154T>C		intron_variant		1	NM_002372.4	ENSP00000261483.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23189 AN: 151696 Hom.: 2001 Cov.: 30

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0310

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.153 AC: 23212 AN: 151814 Hom.: 2004 Cov.: 30 AF XY: 0.150 AC XY: 11098 AN XY: 74190

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0310

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.140

Alfa AF: 0.128 Hom.: 2673

Bravo AF: 0.153

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.91

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: rs6877440; hg19: chr5-109044067;