chr11-134382947-G-A

Variant names:

• chr11-134382947-G-A
• rs115362398
• NM_054025.3:c.681C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_054025.3(B3GAT1):​c.681C>T​(p.Tyr227Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,606,596 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (56 hom.)
• Consequence: B3GAT1 NM_054025.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.536
• Publications: 1 publications found

Genes affected

B3GAT1 (HGNC:921): (beta-1,3-glucuronyltransferase 1) The protein encoded by this gene is a member of the glucuronyltransferase gene family. These enzymes exhibit strict acceptor specificity, recognizing nonreducing terminal sugars and their anomeric linkages. This gene product functions as the key enzyme in a glucuronyl transfer reaction during the biosynthesis of the carbohydrate epitope HNK-1 (human natural killer-1, also known as CD57 and LEU7). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-134382947-G-A is Benign according to our data. Variant chr11-134382947-G-A is described in ClinVar as [Benign]. Clinvar id is 779385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.536 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2148/152190) while in subpopulation AFR AF = 0.0483 (2007/41514). AF 95% confidence interval is 0.0466. There are 61 homozygotes in GnomAd4. There are 1047 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 61 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B3GAT1	NM_054025.3	c.681C>T	p.Tyr227Tyr	synonymous_variant	Exon 4 of 6	ENST00000312527.9	NP_473366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B3GAT1	ENST00000312527.9	c.681C>T	p.Tyr227Tyr	synonymous_variant	Exon 4 of 6	1	NM_054025.3	ENSP00000307875.4
B3GAT1	ENST00000392580.5	c.681C>T	p.Tyr227Tyr	synonymous_variant	Exon 5 of 7	1		ENSP00000376359.1
B3GAT1	ENST00000531778.1	n.3578C>T		non_coding_transcript_exon_variant	Exon 2 of 4	1
B3GAT1	ENST00000524765.1	c.681C>T	p.Tyr227Tyr	synonymous_variant	Exon 4 of 6	2		ENSP00000433847.1

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2118 AN: 152072 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00372 AC: 870 AN: 234150 AF XY: 0.00275

Gnomad AFR exome AF: 0.0510

Gnomad AMR exome AF: 0.00284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000496

Gnomad NFE exome AF: 0.0000574

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.00145 AC: 2115 AN: 1454406 Hom.: 56 Cov.: 32 AF XY: 0.00122 AC XY: 879 AN XY: 722950

African (AFR) AF: 0.0495 AC: 1653 AN: 33378

American (AMR) AF: 0.00342 AC: 149 AN: 43628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39366

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85202

European-Finnish (FIN) AF: 0.0000381 AC: 2 AN: 52560

Middle Eastern (MID) AF: 0.000698 AC: 4 AN: 5734

European-Non Finnish (NFE) AF: 0.0000595 AC: 66 AN: 1108448

Other (OTH) AF: 0.00374 AC: 225 AN: 60110

GnomAD4 genome AF: 0.0141 AC: 2148 AN: 152190 Hom.: 61 Cov.: 33 AF XY: 0.0141 AC XY: 1047 AN XY: 74408

African (AFR) AF: 0.0483 AC: 2007 AN: 41514

American (AMR) AF: 0.00693 AC: 106 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68004

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.00586 Hom.: 18

Bravo AF: 0.0165

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.0
DANN	Benign	0.92
PhyloP100		-0.54
Mutation Taster		=99/1	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: rs115362398; hg19: chr11-134252841;