6-10541595-G-T

Variant names:

• chr6-10541595-G-T
• rs477199
• NM_145649.5:c.925+11759G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145649.5(GCNT2):​c.925+11759G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,072 control chromosomes in the GnomAD database, including 4,375 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 0.20 (4375 hom., cov: 32)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145649.5. 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.925+11759G>T		intron	N/A	NP_663624.1	Q8N0V5-1
	GCNT2	NM_001374747.1		c.925+11759G>T		intron	N/A	NP_001361676.1	Q8N0V5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCNT2	ENST00000495262.7	TSL:2 MANE Select	c.925+11759G>T		intron	N/A	ENSP00000419411.2	Q8N0V5-1
	GCNT2	ENST00000379597.7	TSL:1	c.925+11759G>T		intron	N/A	ENSP00000368917.3	Q8N0V5-1
	GCNT2	ENST00000410107.5	TSL:1	c.67+32437G>T		intron	N/A	ENSP00000386321.1	B7ZBL3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30161 AN: 151954 Hom.: 4355 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.199 AC: 30221 AN: 152072 Hom.: 4375 Cov.: 32 AF XY: 0.197 AC XY: 14608 AN XY: 74336

African (AFR) AF: 0.411 AC: 17034 AN: 41446

American (AMR) AF: 0.114 AC: 1738 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 666 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5184

South Asian (SAS) AF: 0.0874 AC: 421 AN: 4818

European-Finnish (FIN) AF: 0.141 AC: 1492 AN: 10576

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8321 AN: 67992

Other (OTH) AF: 0.162 AC: 341 AN: 2104

Alfa AF: 0.262 Hom.: 1515

Bravo AF: 0.204

Asia WGS AF: 0.0720 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		0.063
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: rs477199; hg19: chr6-10541828;