rs504083

Positions:

• chr6-10540980-G-A
• chr6-10540980-G-C

Variant summary

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

The NM_145649.5(GCNT2):​c.925+11144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,920 control chromosomes in the GnomAD database, including 12,155 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 0.39 (12155 hom., cov: 32)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875

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 = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT2	NM_145649.5	c.925+11144G>A		intron_variant		ENST00000495262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT2	ENST00000495262.7	c.925+11144G>A		intron_variant		2	NM_145649.5	P3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58481 AN: 151798 Hom.: 12126 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.386 AC: 58567 AN: 151920 Hom.: 12155 Cov.: 32 AF XY: 0.381 AC XY: 28267 AN XY: 74224

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.353

Alfa AF: 0.341 Hom.: 13596

Bravo AF: 0.390

Asia WGS AF: 0.311 AC: 1084 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	0.31
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs504083; hg19: chr6-10541213;