rs56394886

Variant names:

• chr11-119027614-G-A
• rs56394886
• NM_001164277.2:c.625+14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001164277.2(SLC37A4):​c.625+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,613,652 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (42 hom., cov: 33)
  • Exomes 𝑓: 0.014 (249 hom.)
• Consequence: SLC37A4 NM_001164277.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0250
• Publications: 2 publications found

Genes affected

SLC37A4 (HGNC:4061): (solute carrier family 37 member 4) This gene regulates glucose-6-phosphate transport from the cytoplasm to the lumen of the endoplasmic reticulum, in order to maintain glucose homeostasis. It also plays a role in ATP-mediated calcium sequestration in the lumen of the endoplasmic reticulum. Mutations in this gene have been associated with various forms of glycogen storage disease. Alternative splicing in this gene results in multiple transcript variants.[provided by RefSeq, Aug 2009]

SLC37A4 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation, type IIw

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• glycogen storage disease Ib

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• glycogen storage disease type 1 due to SLC37A4 mutation

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-119027614-G-A is Benign according to our data. Variant chr11-119027614-G-A is described in ClinVar as Benign. ClinVar VariationId is 139189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164277.2. 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
	SLC37A4	NM_001164277.2	MANE Select	c.625+14C>T		intron	N/A	NP_001157749.1	O43826-1
	SLC37A4	NM_001164278.2		c.625+14C>T		intron	N/A	NP_001157750.1	O43826-2
	SLC37A4	NM_001164280.2		c.625+14C>T		intron	N/A	NP_001157752.1	O43826-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC37A4	ENST00000330775.9	TSL:5	c.625+14C>T		intron	N/A	ENSP00000476242.2	U3KPU7
	SLC37A4	ENST00000524428.5	TSL:1	n.947+14C>T		intron	N/A
	SLC37A4	ENST00000525039.5	TSL:1	n.1049+14C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2020 AN: 152208 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.00425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00693

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.0179 AC: 4455 AN: 248812 AF XY: 0.0179

Gnomad AFR exome AF: 0.00465

Gnomad AMR exome AF: 0.00898

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.0625

Gnomad FIN exome AF: 0.0468

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0139 AC: 20356 AN: 1461326 Hom.: 249 Cov.: 32 AF XY: 0.0140 AC XY: 10179 AN XY: 726970

African (AFR) AF: 0.00392 AC: 131 AN: 33450

American (AMR) AF: 0.00883 AC: 395 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00249 AC: 65 AN: 26136

East Asian (EAS) AF: 0.0411 AC: 1630 AN: 39688

South Asian (SAS) AF: 0.0179 AC: 1536 AN: 85986

European-Finnish (FIN) AF: 0.0443 AC: 2367 AN: 53382

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0121 AC: 13441 AN: 1111836

Other (OTH) AF: 0.0128 AC: 771 AN: 60370

GnomAD4 genome AF: 0.0133 AC: 2022 AN: 152326 Hom.: 42 Cov.: 33 AF XY: 0.0158 AC XY: 1176 AN XY: 74492

African (AFR) AF: 0.00426 AC: 177 AN: 41562

American (AMR) AF: 0.00686 AC: 105 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.0569 AC: 295 AN: 5182

South Asian (SAS) AF: 0.0182 AC: 88 AN: 4832

European-Finnish (FIN) AF: 0.0520 AC: 552 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0114 AC: 776 AN: 68030

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00919 Hom.: 3

Bravo AF: 0.0107

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Glucose-6-phosphate transport defect (2)
-	-	1	not provided (1)
-	-	1	Phosphate transport defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.88
DANN	Benign	0.67
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs56394886; hg19: chr11-118898324;