rs113787911

Variant names:

• chr22-49918341-AAC-A
• rs113787911
• NM_024105.4:c.-159_-158delGT

Your query was ambiguous. Multiple possible variants found:

• chr22-49918341-AAC-A
• chr22-49918341-AAC-AACAC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024105.4(ALG12):​c.-159_-158delGT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 153,378 control chromosomes in the GnomAD database, including 4,597 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4560 hom., cov: 27)
  • Exomes 𝑓: 0.21 (37 hom.)
• Consequence: ALG12 NM_024105.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71
• Publications: 4 publications found

Genes affected

ALG12 (HGNC:19358): (ALG12 alpha-1,6-mannosyltransferase) This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation. [provided by RefSeq, Jul 2008]

CRELD2 (HGNC:28150): (cysteine rich with EGF like domains 2) Predicted to enable calcium ion binding activity and protein disulfide isomerase activity. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 22-49918341-AAC-A is Benign according to our data. Variant chr22-49918341-AAC-A is described in ClinVar as Likely_benign. ClinVar VariationId is 342067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024105.4. 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
	ALG12	NM_024105.4	MANE Select	c.-159_-158delGT		5_prime_UTR	Exon 1 of 10	NP_077010.1	Q9BV10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG12	ENST00000330817.11	TSL:1 MANE Select	c.-159_-158delGT		5_prime_UTR	Exon 1 of 10	ENSP00000333813.5	Q9BV10
	ALG12	ENST00000905517.1		c.-181_-180delGT		5_prime_UTR	Exon 1 of 10	ENSP00000575576.1
	ALG12	ENST00000905518.1		c.-890_-889delGT		5_prime_UTR	Exon 1 of 10	ENSP00000575577.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35282 AN: 151822 Hom.: 4546 Cov.: 27

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.215 AC: 311 AN: 1448 Hom.: 37 AF XY: 0.227 AC XY: 171 AN XY: 752

African (AFR) AF: 0.409 AC: 27 AN: 66

American (AMR) AF: 0.125 AC: 4 AN: 32

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 15 AN: 62

East Asian (EAS) AF: 0.122 AC: 19 AN: 156

South Asian (SAS) AF: 0.423 AC: 11 AN: 26

European-Finnish (FIN) AF: 0.148 AC: 8 AN: 54

Middle Eastern (MID) AF: 0.333 AC: 4 AN: 12

European-Non Finnish (NFE) AF: 0.216 AC: 208 AN: 962

Other (OTH) AF: 0.192 AC: 15 AN: 78

GnomAD4 genome AF: 0.233 AC: 35329 AN: 151930 Hom.: 4560 Cov.: 27 AF XY: 0.230 AC XY: 17055 AN XY: 74286

African (AFR) AF: 0.349 AC: 14461 AN: 41426

American (AMR) AF: 0.164 AC: 2509 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 814 AN: 3452

East Asian (EAS) AF: 0.0892 AC: 461 AN: 5166

South Asian (SAS) AF: 0.332 AC: 1599 AN: 4818

European-Finnish (FIN) AF: 0.150 AC: 1586 AN: 10596

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.192 AC: 13020 AN: 67862

Other (OTH) AF: 0.214 AC: 452 AN: 2110

Alfa AF: 0.218 Hom.: 473

Bravo AF: 0.232

Asia WGS AF: 0.243 AC: 841 AN: 3466

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=300/0	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: rs113787911; hg19: chr22-50311989; COSMIC: COSV58206052; COSMIC: COSV58206052;