rs557441

Variant names:

• chr6-10528854-T-C
• rs557441
• NM_145649.5:c.-58T>C

Variant summary

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

The NM_145649.5(GCNT2):​c.-58T>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 0.074 in 1,347,906 control chromosomes in the GnomAD database, including 4,143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (597 hom., cov: 32)
  • Exomes 𝑓: 0.073 (3546 hom.)
• Consequence: GCNT2 NM_145649.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.331
• Publications: 4 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=-0.76).
• BP6: Variant 6-10528854-T-C is Benign according to our data. Variant chr6-10528854-T-C is described in ClinVar as Benign. ClinVar VariationId is 1285722.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.

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.-58T>C		5_prime_UTR	Exon 3 of 5	NP_663624.1	Q8N0V5-1
	GCNT2	NM_001374747.1		c.-58T>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	ENST00000495262.7	TSL:2 MANE Select	c.-58T>C		5_prime_UTR	Exon 3 of 5	ENSP00000419411.2	Q8N0V5-1
	GCNT2	ENST00000379597.7	TSL:1	c.-58T>C		5_prime_UTR	Exon 1 of 3	ENSP00000368917.3	Q8N0V5-1
	GCNT2	ENST00000410107.5	TSL:1	c.67+19696T>C		intron	N/A	ENSP00000386321.1	B7ZBL3

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12517 AN: 151890 Hom.: 596 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0517

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0911

GnomAD4 exome AF: 0.0729 AC: 87240 AN: 1195898 Hom.: 3546 Cov.: 17 AF XY: 0.0724 AC XY: 44014 AN XY: 608158

African (AFR) AF: 0.107 AC: 3048 AN: 28386

American (AMR) AF: 0.0413 AC: 1835 AN: 44426

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2937 AN: 24530

East Asian (EAS) AF: 0.00996 AC: 384 AN: 38556

South Asian (SAS) AF: 0.0634 AC: 5133 AN: 80968

European-Finnish (FIN) AF: 0.0553 AC: 2892 AN: 52270

Middle Eastern (MID) AF: 0.0978 AC: 384 AN: 3926

European-Non Finnish (NFE) AF: 0.0766 AC: 66782 AN: 871286

Other (OTH) AF: 0.0746 AC: 3845 AN: 51550

GnomAD4 genome AF: 0.0824 AC: 12520 AN: 152008 Hom.: 597 Cov.: 32 AF XY: 0.0799 AC XY: 5939 AN XY: 74314

African (AFR) AF: 0.109 AC: 4524 AN: 41412

American (AMR) AF: 0.0592 AC: 905 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3468

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5168

South Asian (SAS) AF: 0.0613 AC: 295 AN: 4810

European-Finnish (FIN) AF: 0.0517 AC: 548 AN: 10590

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.0808 AC: 5494 AN: 67966

Other (OTH) AF: 0.0901 AC: 190 AN: 2108

Alfa AF: 0.0803 Hom.: 218

Bravo AF: 0.0823

Asia WGS AF: 0.0310 AC: 107 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	-0.76
CADD	Benign	5.2
DANN	Benign	0.75
PhyloP100		-0.33
PromoterAI		-0.094	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs557441; hg19: chr6-10529087;