rs17576994

Positions:

• chr6-10599301-G-A
• chr6-10599301-G-T

Variant summary

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

The ENST00000316170.9(GCNT2):​c.920-22050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,002 control chromosomes in the GnomAD database, including 18,806 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 0.50 (18806 hom., cov: 32)
• Consequence: GCNT2 ENST00000316170.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCNT2	NM_001491.3	c.920-22050G>A		intron_variant		ENST00000316170.9	NP_001482.1
GCNT2	NM_145649.5	c.926-22050G>A		intron_variant		ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000316170.9	c.920-22050G>A		intron_variant		1	NM_001491.3	ENSP00000314844
GCNT2	ENST00000495262.7	c.926-22050G>A		intron_variant		2	NM_145649.5	ENSP00000419411	P3

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75316 AN: 151884 Hom.: 18788 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.496 AC: 75377 AN: 152002 Hom.: 18806 Cov.: 32 AF XY: 0.502 AC XY: 37301 AN XY: 74320

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.507

Alfa AF: 0.469 Hom.: 22991

Bravo AF: 0.506

Asia WGS AF: 0.540 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs17576994; hg19: chr6-10599534;