NM_001491.3:c.330G>A

Variant names:

• chr6-10556753-G-A
• rs35537333
• NM_001491.3:c.330G>A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001491.3(GCNT2):​c.330G>A​(p.Arg110Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,614,018 control chromosomes in the GnomAD database, including 519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (31 hom., cov: 32)
  • Exomes 𝑓: 0.024 (488 hom.)
• Consequence: GCNT2 NM_001491.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.157

Genes affected

GCNT2 (HGNC:4204): (glucosaminyl (N-acetyl) transferase 2 (I blood group)) This gene encodes the enzyme responsible for formation of the blood group I antigen. The i and I antigens are distinguished by linear and branched poly-N-acetyllactosaminoglycans, respectively. The encoded protein is the I-branching enzyme, a beta-1,6-N-acetylglucosaminyltransferase responsible for the conversion of fetal i antigen to adult I antigen in erythrocytes during embryonic development. Mutations in this gene have been associated with adult i blood group phenotype. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 6-10556753-G-A is Benign according to our data. Variant chr6-10556753-G-A is described in ClinVar as [Benign]. Clinvar id is 354703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.157 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0167 (2539/152254) while in subpopulation NFE AF= 0.0265 (1805/68010). AF 95% confidence interval is 0.0255. There are 31 homozygotes in gnomad4. There are 1209 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 31 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_001491.3	c.330G>A	p.Arg110Arg	synonymous_variant	Exon 1 of 3	ENST00000316170.9	NP_001482.1
GCNT2	NM_145649.5	c.925+26917G>A		intron_variant	Intron 3 of 4	ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000316170.9	c.330G>A	p.Arg110Arg	synonymous_variant	Exon 1 of 3	1	NM_001491.3	ENSP00000314844.3
GCNT2	ENST00000495262.7	c.925+26917G>A		intron_variant	Intron 3 of 4	2	NM_145649.5	ENSP00000419411.2

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2539 AN: 152136 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.00439

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00891

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0169 AC: 4258 AN: 251298 Hom.: 56 AF XY: 0.0177 AC XY: 2410 AN XY: 135814

Gnomad AFR exome AF: 0.00443

Gnomad AMR exome AF: 0.00702

Gnomad ASJ exome AF: 0.00893

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0118

Gnomad FIN exome AF: 0.0290

Gnomad NFE exome AF: 0.0244

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0239 AC: 34992 AN: 1461764 Hom.: 488 Cov.: 33 AF XY: 0.0236 AC XY: 17198 AN XY: 727192

Gnomad4 AFR exome AF: 0.00338

Gnomad4 AMR exome AF: 0.00742

Gnomad4 ASJ exome AF: 0.00803

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0123

Gnomad4 FIN exome AF: 0.0289

Gnomad4 NFE exome AF: 0.0274

Gnomad4 OTH exome AF: 0.0211

GnomAD4 genome AF: 0.0167 AC: 2539 AN: 152254 Hom.: 31 Cov.: 32 AF XY: 0.0162 AC XY: 1209 AN XY: 74430

Gnomad4 AFR AF: 0.00438

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00892

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0221 Hom.: 21

Bravo AF: 0.0150

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0237

EpiControl AF: 0.0213

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 13 with adult I phenotype Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Blood group, I system Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Mar 29, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35537333; hg19: chr6-10556986;