chr21-42562889-A-G

Variant names:

• chr21-42562889-A-G
• rs228099
• NM_001320537.2:c.1072+721A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018964.4(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_018964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018964.4. 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
	SLC37A1	NM_001320537.2	MANE Select	c.1072+721A>G		intron	N/A	NP_001307466.1
	SLC37A1	NM_018964.4		c.1072+721A>G		intron	N/A	NP_061837.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC37A1	ENST00000352133.3	TSL:1 MANE Select	c.1072+721A>G		intron	N/A	ENSP00000344648.2
	SLC37A1	ENST00000398341.7	TSL:1	c.1072+721A>G		intron	N/A	ENSP00000381383.3
	SLC37A1	ENST00000893156.1		c.1171+721A>G		intron	N/A	ENSP00000563215.1

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

African (AFR) AF: 0.461 AC: 19072 AN: 41364

American (AMR) AF: 0.691 AC: 10547 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1939 AN: 3472

East Asian (EAS) AF: 0.163 AC: 843 AN: 5162

South Asian (SAS) AF: 0.485 AC: 2332 AN: 4806

European-Finnish (FIN) AF: 0.514 AC: 5405 AN: 10506

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41254 AN: 67900

Other (OTH) AF: 0.565 AC: 1194 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.19
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs228099; hg19: chr21-43982999;