rs228099

Positions:

• chr21-42562889-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320537.2(SLC37A1):​c.1072+721A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,786 control chromosomes in the GnomAD database, including 23,811 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23811 hom., cov: 30)
• Consequence: SLC37A1 NM_001320537.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

SLC37A1 (HGNC:11024): (solute carrier family 37 member 1) The protein encoded by this gene localizes to the endoplasmic reticulum (ER) membrane. This protein translocates glucose-6-phosphate from the cytoplasm into the lumen of the ER for hydrolysis into glucose by another ER membrane protein. This gene is a member of the solute carrier 37 gene family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A1	NM_001320537.2	c.1072+721A>G		intron_variant		ENST00000352133.3	NP_001307466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A1	ENST00000352133.3	c.1072+721A>G		intron_variant		1	NM_001320537.2	ENSP00000344648	P1
SLC37A1	ENST00000398341.7	c.1072+721A>G		intron_variant		1		ENSP00000381383	P1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83218 AN: 151668 Hom.: 23793 Cov.: 30

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.568

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 83286 AN: 151786 Hom.: 23811 Cov.: 30 AF XY: 0.544 AC XY: 40333 AN XY: 74146

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.565

Alfa AF: 0.572 Hom.: 3144

Bravo AF: 0.555

Asia WGS AF: 0.352 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.19

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: rs228099; hg19: chr21-43982999;