NM_007255.3:c.50+14G>C

Variant names:

• chr5-177600274-G-C
• rs1767809097
• NM_007255.3:c.50+14G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007255.3(B4GALT7):​c.50+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000085 in 1,176,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: B4GALT7 NM_007255.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 0 publications found

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, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Ehlers-Danlos syndrome, spondylodysplastic type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007255.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT7	NM_007255.3	MANE Select	c.50+14G>C		intron	N/A	NP_009186.1	Q9UBV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT7	ENST00000029410.10	TSL:1 MANE Select	c.50+14G>C		intron	N/A	ENSP00000029410.5	Q9UBV7
	B4GALT7	ENST00000871348.1		c.50+14G>C		intron	N/A	ENSP00000541407.1
	B4GALT7	ENST00000966184.1		c.50+14G>C		intron	N/A	ENSP00000636243.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.50e-7 AC: 1 AN: 1176922 Hom.: 0 Cov.: 30 AF XY: 0.00000175 AC XY: 1 AN XY: 570578

African (AFR) AF: 0.00 AC: 0 AN: 23892

American (AMR) AF: 0.00 AC: 0 AN: 13684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17554

East Asian (EAS) AF: 0.00 AC: 0 AN: 27074

South Asian (SAS) AF: 0.00 AC: 0 AN: 49916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3318

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 967212

Other (OTH) AF: 0.00 AC: 0 AN: 47372

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.72
PromoterAI		-0.0082	Neutral

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: rs1767809097; hg19: chr5-177027275;