chr6-10528561-T-C

Variant names:

• chr6-10528561-T-C
• rs560194
• ENST00000379597.7:c.-351T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001374747.1(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 NM_001374747.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65
• Publications: 15 publications found

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]

GCNT2 Gene-Disease associations (from GenCC):

• cataract 13 with adult I phenotype

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374747.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	NM_145649.5	MANE Select	c.-281-70T>C		intron	N/A	NP_663624.1	Q8N0V5-1
	GCNT2	NM_001374747.1		c.-351T>C		5_prime_UTR	Exon 1 of 3	NP_001361676.1	Q8N0V5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	ENST00000379597.7	TSL:1	c.-351T>C		5_prime_UTR	Exon 1 of 3	ENSP00000368917.3	Q8N0V5-1
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.-281-70T>C		intron	N/A	ENSP00000419411.2	Q8N0V5-1
	GCNT2	ENST00000410107.5	TSL:1	c.67+19403T>C		intron	N/A	ENSP00000386321.1	B7ZBL3

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

African (AFR) AF: 0.549 AC: 3458 AN: 6304

American (AMR) AF: 0.515 AC: 4479 AN: 8694

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 3089 AN: 5320

East Asian (EAS) AF: 0.603 AC: 5977 AN: 9914

South Asian (SAS) AF: 0.693 AC: 21535 AN: 31076

European-Finnish (FIN) AF: 0.510 AC: 4349 AN: 8528

Middle Eastern (MID) AF: 0.592 AC: 452 AN: 764

European-Non Finnish (NFE) AF: 0.526 AC: 61767 AN: 117462

Other (OTH) AF: 0.538 AC: 5573 AN: 10368

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

African (AFR) AF: 0.562 AC: 23284 AN: 41460

American (AMR) AF: 0.534 AC: 8165 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2031 AN: 3470

East Asian (EAS) AF: 0.594 AC: 3065 AN: 5156

South Asian (SAS) AF: 0.709 AC: 3419 AN: 4824

European-Finnish (FIN) AF: 0.519 AC: 5476 AN: 10544

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36164 AN: 67940

Other (OTH) AF: 0.532 AC: 1118 AN: 2102

Alfa AF: 0.537 Hom.: 60805

Bravo AF: 0.545

Asia WGS AF: 0.612 AC: 2126 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.025
DANN	Benign	0.45
PhyloP100		-1.7
PromoterAI		0.00080	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs560194; hg19: chr6-10528794;