chr6-10601433-G-C

Variant names:

• chr6-10601433-G-C
• rs9460922
• NM_145649.5:c.926-19918G>C

Variant summary

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

The NM_145649.5(GCNT2):​c.926-19918G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,104 control chromosomes in the GnomAD database, including 5,025 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 0.17 (5025 hom., cov: 32)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_145649.5	c.926-19918G>C		intron_variant	Intron 3 of 4	ENST00000495262.7	NP_663624.1
GCNT2	NM_001491.3	c.920-19918G>C		intron_variant	Intron 1 of 2	ENST00000316170.9	NP_001482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7	c.926-19918G>C		intron_variant	Intron 3 of 4	2	NM_145649.5	ENSP00000419411.2
GCNT2	ENST00000316170.9	c.920-19918G>C		intron_variant	Intron 1 of 2	1	NM_001491.3	ENSP00000314844.3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25036 AN: 151986 Hom.: 4998 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.165 AC: 25118 AN: 152104 Hom.: 5025 Cov.: 32 AF XY: 0.159 AC XY: 11849 AN XY: 74360

African (AFR) AF: 0.483 AC: 20019 AN: 41432

American (AMR) AF: 0.0852 AC: 1302 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5180

South Asian (SAS) AF: 0.0421 AC: 203 AN: 4818

European-Finnish (FIN) AF: 0.0286 AC: 303 AN: 10606

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0395 AC: 2684 AN: 67998

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.0346 Hom.: 94

Bravo AF: 0.184

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		0.032
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9460922; hg19: chr6-10601666;