Genetic Variant B4GALT7:c.50+14G>A (chr5-177600274-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_007255.3(B4GALT7):c.50+14G>A 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

B4GALT7
NM_007255.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.717

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

B4GALT7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 5-177600274-G-A is Benign according to our data. Variant chr5-177600274-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2746989.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
B4GALT7	NM_007255.3 link	c.50+14G>A	intron_variant	Intron 1 of 5	ENST00000029410.10	NP_009186.1	Q9UBV7
B4GALT7	XM_047416681.1 link	c.-1061+14G>A	intron_variant	Intron 1 of 6		XP_047272637.1
B4GALT7	XM_047416682.1 link	c.-346+14G>A	intron_variant	Intron 1 of 6		XP_047272638.1
B4GALT7	XM_047416680.1 link	c.-2212G>A	upstream_gene_variant			XP_047272636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALT7	ENST00000029410.10 link	c.50+14G>A		intron_variant	Intron 1 of 5	1	NM_007255.3	ENSP00000029410.5		Q9UBV7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.50e-7

AC:

AN:

1176922

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

570578

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:

AN:

23892

American (AMR)

AF:

0.00

AC:

AN:

13684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17554

East Asian (EAS)

AF:

0.00

AC:

AN:

27074

South Asian (SAS)

AF:

0.00

AC:

AN:

49916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3318

European-Non Finnish (NFE)

AF:

0.00000103

AC:

AN:

967212

Other (OTH)

AF:

0.00

AC:

AN:

47372

⚠️ 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

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Benign:1

Dec 15, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

0.72

PromoterAI

-0.027

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over