5-177600185-C-T

Position:

• chr5-177600185-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.417

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
B4GALT7	NM_007255.3	c.-26C>T		5_prime_UTR_variant	1/6	ENST00000029410.10
B4GALT7	XM_047416681.1	c.-1136C>T		5_prime_UTR_variant	1/7
B4GALT7	XM_047416682.1	c.-421C>T		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
B4GALT7	ENST00000029410.10	c.-26C>T		5_prime_UTR_variant	1/6	1	NM_007255.3	P1

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 321 AN: 151620 Hom.: 1 Cov.: 32

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: 71 AN: 43976 Hom.: 0 AF XY: 0.00195 AC XY: 51 AN XY: 26202

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.: 10 Cov.: 30 AF XY: 0.00364 AC XY: 2114 AN XY: 580118

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.: 1 Cov.: 32 AF XY: 0.00222 AC XY: 165 AN XY: 74158

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.: 0

Bravo AF: 0.00209

Asia WGS AF: 0.000290 AC: 1 AN: 3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 30, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
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

Other links and lift over

dbSNP: rs530248269; hg19: chr5-177027186;