chr5-177600185-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007255.3(B4GALT7):c.-26C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,342,070 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 10 hom. )

Consequence

B4GALT7
NM_007255.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.417

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 5-177600185-C-T is Benign according to our data. Variant chr5-177600185-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 384811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00212 (321/151728) while in subpopulation NFE AF= 0.00351 (238/67842). AF 95% confidence interval is 0.00314. There are 1 homozygotes in gnomad4. There are 165 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
B4GALT7	NM_007255.3 link	c.-26C>T	5_prime_UTR_variant	Exon 1 of 6	ENST00000029410.10	NP_009186.1	Q9UBV7
B4GALT7	XM_047416681.1 link	c.-1136C>T	5_prime_UTR_variant	Exon 1 of 7		XP_047272637.1
B4GALT7	XM_047416682.1 link	c.-421C>T	5_prime_UTR_variant	Exon 1 of 7		XP_047272638.1
B4GALT7	XM_047416680.1 link	c.-2301C>T	upstream_gene_variant			XP_047272636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
B4GALT7	ENST00000029410 link	c.-26C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_007255.3	ENSP00000029410.5		Q9UBV7

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

321

AN:

151620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000774

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000479

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00351

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00161

AC:

AN:

43976

Hom.:

AF XY:

0.00195

AC XY:

AN XY:

26202

show subpopulations

Gnomad AFR exome

AF:

0.00171

Gnomad AMR exome

AF:

0.000610

Gnomad ASJ exome

AF:

0.000520

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00369

AC:

4387

AN:

1190342

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

2114

AN XY:

580118

show subpopulations

Gnomad4 AFR exome

AF:

0.000533

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.000698

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000910

Gnomad4 FIN exome

AF:

0.000510

Gnomad4 NFE exome

AF:

0.00425

Gnomad4 OTH exome

AF:

0.00298

GnomAD4 genome

AF:

0.00212

AC:

321

AN:

151728

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.000772

Gnomad4 AMR

AF:

0.00210

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000479

Gnomad4 NFE

AF:

0.00351

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000849

Hom.:

Bravo

AF:

0.00209

Asia WGS

AF:

0.000290

AC:

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 30, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over