rs741811

Variant names:

• chr11-119027609-G-A
• rs741811
• NM_001164277.2:c.625+19C>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+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,258 control chromosomes in the GnomAD database, including 12,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1037 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11469 hom.)
• Consequence: SLC37A4 NM_001164277.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0310
• Publications: 17 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=-0.81).
• BP6: Variant 11-119027609-G-A is Benign according to our data. Variant chr11-119027609-G-A is described in ClinVar as Benign. ClinVar VariationId is 139190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 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+19C>T		intron	N/A	NP_001157749.1	O43826-1
	SLC37A4	NM_001164278.2		c.625+19C>T		intron	N/A	NP_001157750.1	O43826-2
	SLC37A4	NM_001164280.2		c.625+19C>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+19C>T		intron	N/A	ENSP00000476242.2	U3KPU7
	SLC37A4	ENST00000524428.5	TSL:1	n.947+19C>T		intron	N/A
	SLC37A4	ENST00000525039.5	TSL:1	n.1049+19C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16741 AN: 152140 Hom.: 1038 Cov.: 33

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.106 AC: 26270 AN: 248416 AF XY: 0.108

Gnomad AFR exome AF: 0.0816

Gnomad AMR exome AF: 0.0862

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0110

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.123 AC: 179252 AN: 1461000 Hom.: 11469 Cov.: 32 AF XY: 0.122 AC XY: 88917 AN XY: 726784

African (AFR) AF: 0.0827 AC: 2764 AN: 33442

American (AMR) AF: 0.0925 AC: 4133 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3841 AN: 26134

East Asian (EAS) AF: 0.0189 AC: 749 AN: 39678

South Asian (SAS) AF: 0.0886 AC: 7608 AN: 85916

European-Finnish (FIN) AF: 0.118 AC: 6304 AN: 53366

Middle Eastern (MID) AF: 0.149 AC: 859 AN: 5768

European-Non Finnish (NFE) AF: 0.131 AC: 145384 AN: 1111636

Other (OTH) AF: 0.126 AC: 7610 AN: 60358

GnomAD4 genome AF: 0.110 AC: 16743 AN: 152258 Hom.: 1037 Cov.: 33 AF XY: 0.108 AC XY: 8038 AN XY: 74438

African (AFR) AF: 0.0826 AC: 3429 AN: 41536

American (AMR) AF: 0.127 AC: 1943 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3470

East Asian (EAS) AF: 0.0135 AC: 70 AN: 5188

South Asian (SAS) AF: 0.0888 AC: 429 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1306 AN: 10592

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8725 AN: 68016

Other (OTH) AF: 0.132 AC: 280 AN: 2116

Alfa AF: 0.123 Hom.: 2111

Bravo AF: 0.109

Asia WGS AF: 0.0590 AC: 207 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	-0.81
CADD	Benign	0.16
DANN	Benign	0.62
PhyloP100		-0.031
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs741811; hg19: chr11-118898319;