chr6-10528561-T-C

Position:

• chr6-10528561-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000379597.7(GCNT2):​c.-351T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 350,408 control chromosomes in the GnomAD database, including 54,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (23075 hom., cov: 32)
  • Exomes 𝑓: 0.56 (31648 hom.)
• Consequence: GCNT2 ENST00000379597.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-10528561-T-C is Benign according to our data. Variant chr6-10528561-T-C is described in ClinVar as [Benign]. Clinvar id is 1286956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCNT2	NM_145649.5	c.-281-70T>C		intron_variant		ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7	c.-281-70T>C		intron_variant		2	NM_145649.5	ENSP00000419411	P3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83397 AN: 151860 Hom.: 23052 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.558 AC: 110679 AN: 198430 Hom.: 31648 Cov.: 0 AF XY: 0.571 AC XY: 60837 AN XY: 106552

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.581

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.693

Gnomad4 FIN exome AF: 0.510

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.549 AC: 83456 AN: 151978 Hom.: 23075 Cov.: 32 AF XY: 0.552 AC XY: 40953 AN XY: 74242

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.594

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.532

Alfa AF: 0.532 Hom.: 23920

Bravo AF: 0.545

Asia WGS AF: 0.612 AC: 2126 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.025
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs560194; hg19: chr6-10528794;