rs2298475

Variant names:

• chr11-126408308-T-C
• rs2298475
• NM_001254757.2:c.439T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-126408308-T-C
• chr11-126408308-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001254757.2(ST3GAL4):​c.439T>C​(p.Leu147Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 1,613,794 control chromosomes in the GnomAD database, including 5,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.073 (577 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5362 hom.)
• Consequence: ST3GAL4 NM_001254757.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002615
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.657
• Publications: 15 publications found

Genes affected

ST3GAL4 (HGNC:10864): (ST3 beta-galactoside alpha-2,3-sialyltransferase 4) This gene encodes a member of the glycosyltransferase 29 family, a group of enzymes involved in protein glycosylation. The encoded protein is targeted to Golgi membranes but may be proteolytically processed and secreted. The gene product may also be involved in the increased expression of sialyl Lewis X antigen seen in inflammatory responses. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-126408308-T-C is Benign according to our data. Variant chr11-126408308-T-C is described in ClinVar as Benign. ClinVar VariationId is 257675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.657 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001254757.2. 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
	ST3GAL4	NM_001254757.2	MANE Select	c.439T>C	p.Leu147Leu	splice_region synonymous	Exon 8 of 11	NP_001241686.1	Q11206-1
	ST3GAL4	NM_001348396.2		c.502T>C	p.Leu168Leu	splice_region synonymous	Exon 9 of 12	NP_001335325.1	A0A7P0RGI5
	ST3GAL4	NM_001348397.2		c.502T>C	p.Leu168Leu	splice_region synonymous	Exon 9 of 12	NP_001335326.1	A0A7P0RGI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST3GAL4	ENST00000444328.7	TSL:5 MANE Select	c.439T>C	p.Leu147Leu	splice_region synonymous	Exon 8 of 11	ENSP00000394354.2	Q11206-1
	ST3GAL4	ENST00000392669.6	TSL:1	c.439T>C	p.Leu147Leu	splice_region synonymous	Exon 8 of 11	ENSP00000376437.2	Q11206-1
	ST3GAL4	ENST00000526727.5	TSL:1	c.439T>C	p.Leu147Leu	splice_region synonymous	Exon 7 of 10	ENSP00000436047.1	Q11206-1

Frequencies

GnomAD3 genomes AF: 0.0726 AC: 11040 AN: 152042 Hom.: 575 Cov.: 32

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0608

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0761

GnomAD2 exomes AF: 0.0865 AC: 21748 AN: 251306 AF XY: 0.0841

Gnomad AFR exome AF: 0.0200

Gnomad AMR exome AF: 0.0993

Gnomad ASJ exome AF: 0.0425

Gnomad EAS exome AF: 0.211

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.0805

Gnomad OTH exome AF: 0.0814

GnomAD4 exome AF: 0.0793 AC: 115884 AN: 1461634 Hom.: 5362 Cov.: 34 AF XY: 0.0785 AC XY: 57092 AN XY: 727070

African (AFR) AF: 0.0183 AC: 612 AN: 33478

American (AMR) AF: 0.0970 AC: 4337 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0432 AC: 1128 AN: 26134

East Asian (EAS) AF: 0.220 AC: 8743 AN: 39688

South Asian (SAS) AF: 0.0575 AC: 4961 AN: 86254

European-Finnish (FIN) AF: 0.104 AC: 5543 AN: 53418

Middle Eastern (MID) AF: 0.0508 AC: 293 AN: 5766

European-Non Finnish (NFE) AF: 0.0772 AC: 85834 AN: 1111782

Other (OTH) AF: 0.0734 AC: 4433 AN: 60392

GnomAD4 genome AF: 0.0726 AC: 11043 AN: 152160 Hom.: 577 Cov.: 32 AF XY: 0.0773 AC XY: 5748 AN XY: 74400

African (AFR) AF: 0.0223 AC: 925 AN: 41536

American (AMR) AF: 0.113 AC: 1720 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5158

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4816

European-Finnish (FIN) AF: 0.111 AC: 1181 AN: 10602

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5505 AN: 67976

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0754 Hom.: 1670

Bravo AF: 0.0698

Asia WGS AF: 0.122 AC: 422 AN: 3478

EpiCase AF: 0.0736

EpiControl AF: 0.0734

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.53
DANN	Benign	0.49
PhyloP100		-0.66
Mutation Taster		=76/24	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00026
dbscSNV1_RF	Benign	0.040
SpliceAI score (max)		0.010		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: rs2298475; hg19: chr11-126278203; COSMIC: COSV57106578; COSMIC: COSV57106578;