rs1190625

Variant names:

• chr11-66346559-G-A
• rs1190625
• NM_006876.3:c.987C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-66346559-G-A
• chr11-66346559-G-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_006876.3(B4GAT1):​c.987C>T​(p.Tyr329Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000604 in 1,613,746 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (6 hom.)
• Consequence: B4GAT1 NM_006876.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.456
• Publications: 0 publications found

Genes affected

B4GAT1 (HGNC:15685): (beta-1,4-glucuronyltransferase 1) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase family. This enzyme is a type II transmembrane protein. It is essential for the synthesis of poly-N-acetyllactosamine, a determinant for the blood group i antigen. [provided by RefSeq, Jul 2008]

B4GAT1 Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 11-66346559-G-A is Benign according to our data. Variant chr11-66346559-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 420609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.456 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00297 (453/152294) while in subpopulation AFR AF = 0.0103 (427/41554). AF 95% confidence interval is 0.00947. There are 2 homozygotes in GnomAd4. There are 213 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GAT1	NM_006876.3	c.987C>T	p.Tyr329Tyr	synonymous_variant	Exon 1 of 2	ENST00000311181.5	NP_006867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GAT1	ENST00000311181.5	c.987C>T	p.Tyr329Tyr	synonymous_variant	Exon 1 of 2	1	NM_006876.3	ENSP00000309096.4

Frequencies

GnomAD3 genomes AF: 0.00297 AC: 452 AN: 152176 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00334

GnomAD2 exomes AF: 0.000726 AC: 182 AN: 250846 AF XY: 0.000545

Gnomad AFR exome AF: 0.00958

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000357 AC: 522 AN: 1461452 Hom.: 6 Cov.: 32 AF XY: 0.000305 AC XY: 222 AN XY: 727012

African (AFR) AF: 0.0120 AC: 403 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53218

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111816

Other (OTH) AF: 0.000845 AC: 51 AN: 60380

GnomAD4 genome AF: 0.00297 AC: 453 AN: 152294 Hom.: 2 Cov.: 32 AF XY: 0.00286 AC XY: 213 AN XY: 74460

African (AFR) AF: 0.0103 AC: 427 AN: 41554

American (AMR) AF: 0.000653 AC: 10 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.00332

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

B4GAT1: BP4, BP7, BS1 -

Dec 30, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13 Benign:1

Jan 23, 2025

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	7.0
DANN	Benign	0.89
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs1190625; hg19: chr11-66114030;