rs2306760

Variant names:

• chr5-177600404-T-C
• rs2306760
• NM_007255.3:c.50+144T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007255.3(B4GALT7):​c.50+144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 600,386 control chromosomes in the GnomAD database, including 4,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (1094 hom., cov: 31)
  • Exomes 𝑓: 0.10 (3246 hom.)
• Consequence: B4GALT7 NM_007255.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.441
• Publications: 1 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, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
• Ehlers-Danlos syndrome, spondylodysplastic type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-177600404-T-C is Benign according to our data. Variant chr5-177600404-T-C is described in ClinVar as [Benign]. Clinvar id is 1246191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
B4GALT7	NM_007255.3	c.50+144T>C		intron_variant	Intron 1 of 5	ENST00000029410.10	NP_009186.1
B4GALT7	XM_047416680.1	c.-2082T>C		5_prime_UTR_variant	Exon 1 of 6		XP_047272636.1
B4GALT7	XM_047416681.1	c.-1061+144T>C		intron_variant	Intron 1 of 6		XP_047272637.1
B4GALT7	XM_047416682.1	c.-346+144T>C		intron_variant	Intron 1 of 6		XP_047272638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALT7	ENST00000029410.10	c.50+144T>C		intron_variant	Intron 1 of 5	1	NM_007255.3	ENSP00000029410.5

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14424 AN: 151974 Hom.: 1091 Cov.: 31

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0863

Gnomad OTH AF: 0.120

GnomAD4 exome AF: 0.0999 AC: 44796 AN: 448294 Hom.: 3246 AF XY: 0.100 AC XY: 22160 AN XY: 221702

African (AFR) AF: 0.0232 AC: 240 AN: 10364

American (AMR) AF: 0.179 AC: 1232 AN: 6866

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 2356 AN: 9378

East Asian (EAS) AF: 0.322 AC: 7175 AN: 22272

South Asian (SAS) AF: 0.101 AC: 925 AN: 9154

European-Finnish (FIN) AF: 0.117 AC: 2344 AN: 19962

Middle Eastern (MID) AF: 0.181 AC: 341 AN: 1882

European-Non Finnish (NFE) AF: 0.0795 AC: 27553 AN: 346702

Other (OTH) AF: 0.121 AC: 2630 AN: 21714

GnomAD4 genome AF: 0.0949 AC: 14432 AN: 152092 Hom.: 1094 Cov.: 31 AF XY: 0.0997 AC XY: 7409 AN XY: 74330

African (AFR) AF: 0.0236 AC: 980 AN: 41546

American (AMR) AF: 0.193 AC: 2948 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3466

East Asian (EAS) AF: 0.307 AC: 1565 AN: 5096

South Asian (SAS) AF: 0.117 AC: 564 AN: 4808

European-Finnish (FIN) AF: 0.112 AC: 1184 AN: 10590

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.0863 AC: 5868 AN: 68000

Other (OTH) AF: 0.125 AC: 265 AN: 2112

Alfa AF: 0.0967 Hom.: 1940

Bravo AF: 0.102

Asia WGS AF: 0.239 AC: 828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

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	-0.81
CADD	Benign	7.8
DANN	Benign	0.84
PhyloP100		-0.44
PromoterAI		0.026	Neutral
Mutation Taster		=100/0	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: rs2306760; hg19: chr5-177027405;