rs1087924

Positions:

• chr6-10523593-G-C
• chr6-10523593-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.-469+2176G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,826 control chromosomes in the GnomAD database, including 23,160 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 0.55 (23160 hom., cov: 31)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT2	NM_145649.5	c.-469+2176G>C		intron_variant		ENST00000495262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT2	ENST00000495262.7	c.-469+2176G>C		intron_variant		2	NM_145649.5	P3

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83586 AN: 151708 Hom.: 23140 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.551 AC: 83648 AN: 151826 Hom.: 23160 Cov.: 31 AF XY: 0.554 AC XY: 41070 AN XY: 74196

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.528

Alfa AF: 0.530 Hom.: 2571

Bravo AF: 0.546

Asia WGS AF: 0.609 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.8
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1087924; hg19: chr6-10523826;