rs504083

Variant names:

• chr6-10540980-G-A
• rs504083
• NM_145649.5:c.925+11144G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-10540980-G-A
• chr6-10540980-G-C
• chr6-10540980-G-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+11144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,920 control chromosomes in the GnomAD database, including 12,155 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 0.39 (12155 hom., cov: 32)
• Consequence: GCNT2 NM_145649.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT2	NM_145649.5	c.925+11144G>A		intron_variant	Intron 3 of 4	ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7	c.925+11144G>A		intron_variant	Intron 3 of 4	2	NM_145649.5	ENSP00000419411.2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58481 AN: 151798 Hom.: 12126 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.386 AC: 58567 AN: 151920 Hom.: 12155 Cov.: 32 AF XY: 0.381 AC XY: 28267 AN XY: 74224

African (AFR) AF: 0.556 AC: 23035 AN: 41416

American (AMR) AF: 0.280 AC: 4267 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1365 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1333 AN: 5166

South Asian (SAS) AF: 0.298 AC: 1434 AN: 4814

European-Finnish (FIN) AF: 0.292 AC: 3083 AN: 10544

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22989 AN: 67962

Other (OTH) AF: 0.353 AC: 746 AN: 2112

Alfa AF: 0.353 Hom.: 34359

Bravo AF: 0.390

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.31
DANN	Benign	0.68
PhyloP100		-0.88
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: rs504083; hg19: chr6-10541213;