5-177600264-AGCG-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000029410.10(B4GALT7):​c.50+5_50+7delGCG variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000837 in 1,194,720 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

B4GALT7
ENST00000029410.10 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.04

Publications

0 publications found
Variant links:
Genes affected
B4GALT7 (HGNC:930): (beta-1,4-galactosyltransferase 7) This gene is a member of the beta-1,4-galactosyltransferase (beta4GalT) family. Family members encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. Each beta4GalT member has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus which then remains uncleaved to function as a transmembrane anchor. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage (GlcA-beta1,3-Gal-beta1,3-Gal-beta1,4-Xyl-beta1-O-Ser) found in proteoglycans. This enzyme differs from other beta4GalTs because it lacks the conserved Cys residues found in beta4GalT1-beta4GalT6 and it is located in cis-Golgi instead of trans-Golgi. Mutations in this gene have been associated with the progeroid form of Ehlers-Danlos syndrome. [provided by RefSeq, Oct 2009]
B4GALT7 Gene-Disease associations (from GenCC):
  • Ehlers-Danlos syndrome, spondylodysplastic type, 1
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
  • Ehlers-Danlos syndrome, spondylodysplastic type
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
B4GALT7NM_007255.3 linkc.50+12_50+14delCGG intron_variant Intron 1 of 5 ENST00000029410.10 NP_009186.1 Q9UBV7
B4GALT7XM_047416681.1 linkc.-1061+12_-1061+14delCGG intron_variant Intron 1 of 6 XP_047272637.1
B4GALT7XM_047416682.1 linkc.-346+12_-346+14delCGG intron_variant Intron 1 of 6 XP_047272638.1
B4GALT7XM_047416680.1 linkc.-2221_-2219delGCG upstream_gene_variant XP_047272636.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
B4GALT7ENST00000029410.10 linkc.50+5_50+7delGCG splice_region_variant, intron_variant Intron 1 of 5 1 NM_007255.3 ENSP00000029410.5 Q9UBV7

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.0000291
AC:
1
AN:
34406
AF XY:
0.0000474
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000198
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
8.37e-7
AC:
1
AN:
1194720
Hom.:
0
AF XY:
0.00000172
AC XY:
1
AN XY:
581328
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
24262
American (AMR)
AF:
0.0000617
AC:
1
AN:
16200
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18870
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
53504
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
27714
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3380
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
975594
Other (OTH)
AF:
0.00
AC:
0
AN:
48018
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
4.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs1561812475; hg19: chr5-177027265; API