rs4567

Variant names:

• chr9-137108975-A-G
• rs4567
• NM_016219.5:c.*384A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-137108975-A-G
• chr9-137108975-A-C
• chr9-137108975-A-T

Variant summary

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

The NM_016219.5(MAN1B1):​c.*384A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 464,886 control chromosomes in the GnomAD database, including 57,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19266 hom., cov: 30)
  • Exomes 𝑓: 0.49 (38252 hom.)
• Consequence: MAN1B1 NM_016219.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.72
• Publications: 20 publications found

Genes affected

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: ClinGen, Orphanet
• Rafiq syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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 (REVEL=0.01).
• BP6: Variant 9-137108975-A-G is Benign according to our data. Variant chr9-137108975-A-G is described in ClinVar as Benign. ClinVar VariationId is 365984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016219.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1B1	NM_016219.5	MANE Select	c.*384A>G		3_prime_UTR	Exon 13 of 13	NP_057303.2	Q9UKM7
	MAN1B1	NR_045720.2		n.2474A>G		non_coding_transcript_exon	Exon 13 of 13
	MAN1B1	NR_045721.2		n.2630A>G		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1B1	ENST00000371589.9	TSL:1 MANE Select	c.*384A>G		3_prime_UTR	Exon 13 of 13	ENSP00000360645.4	Q9UKM7
	MAN1B1	ENST00000371587.9	TSL:1	n.*2161A>G		non_coding_transcript_exon	Exon 14 of 14	ENSP00000483132.2	A0A087X064
	MAN1B1	ENST00000544448.6	TSL:1	n.*767A>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000444966.2	H0YGV7

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75727 AN: 151710 Hom.: 19242 Cov.: 30

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.500

GnomAD2 exomes AF: 0.514 AC: 70309 AN: 136668 AF XY: 0.511

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.572

Gnomad ASJ exome AF: 0.529

Gnomad EAS exome AF: 0.716

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.503

GnomAD4 exome AF: 0.489 AC: 152970 AN: 313060 Hom.: 38252 Cov.: 0 AF XY: 0.488 AC XY: 86676 AN XY: 177738

African (AFR) AF: 0.547 AC: 4902 AN: 8956

American (AMR) AF: 0.573 AC: 15742 AN: 27494

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 5905 AN: 11168

East Asian (EAS) AF: 0.715 AC: 6965 AN: 9742

South Asian (SAS) AF: 0.503 AC: 30064 AN: 59796

European-Finnish (FIN) AF: 0.434 AC: 5705 AN: 13160

Middle Eastern (MID) AF: 0.448 AC: 1265 AN: 2826

European-Non Finnish (NFE) AF: 0.456 AC: 75293 AN: 165144

Other (OTH) AF: 0.483 AC: 7129 AN: 14774

GnomAD4 genome AF: 0.499 AC: 75800 AN: 151826 Hom.: 19266 Cov.: 30 AF XY: 0.499 AC XY: 37045 AN XY: 74206

African (AFR) AF: 0.550 AC: 22778 AN: 41394

American (AMR) AF: 0.531 AC: 8108 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1901 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3648 AN: 5144

South Asian (SAS) AF: 0.507 AC: 2434 AN: 4804

European-Finnish (FIN) AF: 0.421 AC: 4453 AN: 10568

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.455 AC: 30909 AN: 67890

Other (OTH) AF: 0.505 AC: 1062 AN: 2102

Alfa AF: 0.469 Hom.: 18539

Bravo AF: 0.514

Asia WGS AF: 0.582 AC: 2025 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Rafiq syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.47
PhyloP100		-4.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4567; hg19: chr9-140003427;