Variant 6-10530003-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145649.5(GCNT2):c.925+167A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 630,822 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 44 hom., cov: 32)

Exomes 𝑓: 0.022 ( 149 hom. )

Consequence

GCNT2
NM_145649.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.521

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-10530003-A-T is Benign according to our data. Variant chr6-10530003-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1215107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0191 (2907/152320) while in subpopulation NFE AF= 0.0285 (1938/68032). AF 95% confidence interval is 0.0274. There are 44 homozygotes in gnomad4. There are 1397 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCNT2	NM_145649.5 linkuse as main transcript	c.925+167A>T		intron_variant		ENST00000495262.7	NP_663624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCNT2	ENST00000495262.7 linkuse as main transcript	c.925+167A>T		intron_variant		2	NM_145649.5	ENSP00000419411	P3	Q8N0V5-1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2909

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00492

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0244

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0243

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0285

Gnomad OTH

AF:

0.0224

GnomAD4 exome

AF:

0.0222

AC:

10633

AN:

478502

Hom.:

149

Cov.:

AF XY:

0.0213

AC XY:

5394

AN XY:

253614

show subpopulations

Gnomad4 AFR exome

AF:

0.00524

Gnomad4 AMR exome

AF:

0.0191

Gnomad4 ASJ exome

AF:

0.0187

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00425

Gnomad4 FIN exome

AF:

0.0232

Gnomad4 NFE exome

AF:

0.0286

Gnomad4 OTH exome

AF:

0.0227

GnomAD4 genome

AF:

0.0191

AC:

2907

AN:

152320

Hom.:

Cov.:

AF XY:

0.0188

AC XY:

1397

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00491

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0243

Gnomad4 NFE

AF:

0.0285

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00858

Hom.:

Bravo

AF:

0.0193

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.88

DANN

Benign

0.59

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over