rs741811

Positions:

• chr11-119027609-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001164278.2(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_001164278.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0310

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A4	NM_001164278.2	c.625+19C>T		intron_variant			NP_001157750.1
SLC37A4	NM_001164277.2	c.625+19C>T		intron_variant			NP_001157749.1
SLC37A4	NM_001164280.2	c.625+19C>T		intron_variant			NP_001157752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9	c.625+19C>T		intron_variant		5		ENSP00000476242.2

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

GnomAD3 exomes AF: 0.106 AC: 26270 AN: 248416 Hom.: 1607 AF XY: 0.108 AC XY: 14581 AN XY: 134814

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 SAS exome AF: 0.0903

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

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.0925

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.0189

Gnomad4 SAS exome AF: 0.0886

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.126

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

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.0888

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.132

Alfa AF: 0.126 Hom.: 1421

Bravo AF: 0.109

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2013	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. -

Glucose-6-phosphate transport defect Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Phosphate transport defect Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.16
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs741811; hg19: chr11-118898319;