9-137086789-G-C

Variant names:

• chr9-137086789-G-C
• rs968732
• ENST00000596585.3:n.29C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NR_027447.1(MAN1B1-DT):​n.29C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 695,842 control chromosomes in the GnomAD database, including 347,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75900 hom., cov: 37)
  • Exomes 𝑓: 1.0 (271574 hom.)
• Consequence: MAN1B1-DT NR_027447.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.09
• Publications: 1 publications found

Genes affected

MAN1B1-DT (HGNC:48715): (MAN1B1 divergent transcript)

MAN1B1 (HGNC:6823): (mannosidase alpha class 1B member 1) This gene encodes an enzyme belonging to the glycosyl hydrolase 47 family. This enzyme functions in N-glycan biosynthesis, and is a class I alpha-1,2-mannosidase that specifically converts Man9GlcNAc to Man8GlcNAc isomer B. It is required for N-glycan trimming to Man5-6GlcNAc2 in the endoplasmic-reticulum-associated degradation pathway. Mutations in this gene cause autosomal-recessive intellectual disability. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Dec 2011]

MAN1B1 Gene-Disease associations (from GenCC):

• MAN1B1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Rafiq syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 9-137086789-G-C is Benign according to our data. Variant chr9-137086789-G-C is described in ClinVar as [Benign]. Clinvar id is 1283979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1B1	NM_016219.5	c.-211G>C		upstream_gene_variant		ENST00000371589.9	NP_057303.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1B1	ENST00000371589.9	c.-211G>C		upstream_gene_variant		1	NM_016219.5	ENSP00000360645.4

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151975 AN: 152270 Hom.: 75841 Cov.: 37

Gnomad AFR AF: 0.993

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.999

GnomAD4 exome AF: 1.00 AC: 543299 AN: 543454 Hom.: 271574 Cov.: 4 AF XY: 1.00 AC XY: 294160 AN XY: 294226

African (AFR) AF: 0.993 AC: 15345 AN: 15456

American (AMR) AF: 1.00 AC: 33372 AN: 33384

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 19304 AN: 19304

East Asian (EAS) AF: 1.00 AC: 31982 AN: 31982

South Asian (SAS) AF: 1.00 AC: 60992 AN: 60996

European-Finnish (FIN) AF: 1.00 AC: 32737 AN: 32738

Middle Eastern (MID) AF: 0.999 AC: 3624 AN: 3626

European-Non Finnish (NFE) AF: 1.00 AC: 315812 AN: 315818

Other (OTH) AF: 0.999 AC: 30131 AN: 30150

GnomAD4 genome AF: 0.998 AC: 152094 AN: 152388 Hom.: 75900 Cov.: 37 AF XY: 0.998 AC XY: 74383 AN XY: 74516

African (AFR) AF: 0.993 AC: 41310 AN: 41590

American (AMR) AF: 0.999 AC: 15306 AN: 15314

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4834 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10632 AN: 10632

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68038 AN: 68042

Other (OTH) AF: 0.999 AC: 2114 AN: 2116

Alfa AF: 1.00 Hom.: 3329

Bravo AF: 0.998

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0050
DANN	Benign	0.37
PhyloP100		-5.1
PromoterAI		-0.049	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs968732; hg19: chr9-139981241;