rs477199

Positions:

• chr6-10541595-G-T

Variant summary

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

The NM_145649.5(GCNT2):​c.925+11759G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,072 control chromosomes in the GnomAD database, including 4,375 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 0.20 (4375 hom., cov: 32)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCNT2	NM_145649.5	c.925+11759G>T		intron_variant		ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7	c.925+11759G>T		intron_variant		2	NM_145649.5	ENSP00000419411	P3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30161 AN: 151954 Hom.: 4355 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.199 AC: 30221 AN: 152072 Hom.: 4375 Cov.: 32 AF XY: 0.197 AC XY: 14608 AN XY: 74336

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.0874

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.162

Alfa AF: 0.177 Hom.: 435

Bravo AF: 0.204

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs477199; hg19: chr6-10541828;