6-10528781-A-G

Position:

• chr6-10528781-A-G

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.-131A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 766,714 control chromosomes in the GnomAD database, including 3,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (788 hom., cov: 32)
  • Exomes 𝑓: 0.092 (2883 hom.)
• Consequence: GCNT2 NM_145649.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.84

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=-0.86).
• BP6: Variant 6-10528781-A-G is Benign according to our data. Variant chr6-10528781-A-G is described in ClinVar as [Benign]. Clinvar id is 1233305.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	Protein	UniProt
GCNT2	NM_145649.5	c.-131A>G		5_prime_UTR_variant	3/5	ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7	c.-131A>G		5_prime_UTR_variant	3/5	2	NM_145649.5	ENSP00000419411	P3

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14786 AN: 152180 Hom.: 788 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0772

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.0906

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0922 AC: 56626 AN: 614416 Hom.: 2883 Cov.: 7 AF XY: 0.0925 AC XY: 30761 AN XY: 332576

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0557

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.0943

Gnomad4 FIN exome AF: 0.0863

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0927

GnomAD4 genome AF: 0.0971 AC: 14788 AN: 152298 Hom.: 788 Cov.: 32 AF XY: 0.0960 AC XY: 7146 AN XY: 74474

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0771

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0971 Hom.: 308

Bravo AF: 0.0954

Asia WGS AF: 0.0420 AC: 145 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 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.66
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs618705; hg19: chr6-10529014;