9-76423254-T-G

Variant names:

• chr9-76423254-T-G
• rs6560517
• NM_001407181.1:c.-744-18607T>G

Variant summary

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

The NM_001407181.1(GCNT1):​c.-744-18607T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,136 control chromosomes in the GnomAD database, including 6,910 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 0.30 (6910 hom., cov: 33)
• Consequence: GCNT1 NM_001407181.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 6 publications found

Genes affected

GCNT1 (HGNC:4203): (glucosaminyl (N-acetyl) transferase 1) This gene is a member of the beta-1,6-N-acetylglucosaminyltransferase gene family. It is essential to the formation of Gal beta 1-3(GlcNAc beta 1-6)GalNAc structures and the core 2 O-glycan branch. The gene coding this enzyme was originally mapped to 9q21, but was later localized to 9q13. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCNT1	NM_001407181.1	c.-744-18607T>G		intron_variant	Intron 2 of 4		NP_001394110.1
GCNT1	NM_001407182.1	c.-290+27683T>G		intron_variant	Intron 2 of 3		NP_001394111.1
GCNT1	NM_001407183.1	c.-290+28834T>G		intron_variant	Intron 1 of 2		NP_001394112.1
GCNT1	NM_001407184.1	c.-290+27683T>G		intron_variant	Intron 2 of 3		NP_001394113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCNT1	ENST00000488136.5	n.38+3367T>G		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45148 AN: 152018 Hom.: 6903 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.297 AC: 45181 AN: 152136 Hom.: 6910 Cov.: 33 AF XY: 0.296 AC XY: 22031 AN XY: 74366

African (AFR) AF: 0.309 AC: 12840 AN: 41518

American (AMR) AF: 0.329 AC: 5013 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1212 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1962 AN: 5166

South Asian (SAS) AF: 0.291 AC: 1408 AN: 4832

European-Finnish (FIN) AF: 0.243 AC: 2577 AN: 10596

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19152 AN: 67982

Other (OTH) AF: 0.323 AC: 682 AN: 2114

Alfa AF: 0.198 Hom.: 1721

Bravo AF: 0.305

Asia WGS AF: 0.313 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.68
PhyloP100		0.28
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: rs6560517; hg19: chr9-79038170;