6-10528854-T-C

Variant summary

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

The NM_145649.5(GCNT2):c.-58T>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 0.074 in 1,347,906 control chromosomes in the GnomAD database, including 4,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (597 hom., cov: 32)
  • Exomes 𝑓: 0.073 (3546 hom.)
• Consequence: GCNT2 NM_145649.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.331

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=-0.76).
• BP6: Variant 6-10528854-T-C is Benign according to our data. Variant chr6-10528854-T-C is described in ClinVar as [Benign]. Clinvar id is 1285722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCNT2	NM_145649.5	c.-58T>C		5_prime_UTR_variant	3/5	ENST00000495262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCNT2	ENST00000495262.7	c.-58T>C		5_prime_UTR_variant	3/5	2	NM_145649.5	P3

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12517 AN: 151890 Hom.: 596 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0911

GnomAD4 exome AF: 0.0729 AC: 87240 AN: 1195898 Hom.: 3546 Cov.: 17 AF XY: 0.0724 AC XY: 44014 AN XY: 608158

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0413

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.00996

Gnomad4 SAS exome AF: 0.0634

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.0746

GnomAD4 genome AF: 0.0824 AC: 12520 AN: 152008 Hom.: 597 Cov.: 32 AF XY: 0.0799 AC XY: 5939 AN XY: 74314

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0613

Gnomad4 FIN AF: 0.0517

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.0901

Alfa AF: 0.0789 Hom.: 170

Bravo AF: 0.0823

Asia WGS AF: 0.0310 AC: 107 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

Oct 02, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	5.2
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs557441; hg19: chr6-10529087;