rs6656822

chr1-169467308-T-C

Variant summary

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

The NM_006996.3(SLC19A2):c.1365+803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,108 control chromosomes in the GnomAD database, including 40,149 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 0.72 (40149 hom., cov: 32)
• Consequence: SLC19A2 NM_006996.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

Genes affected

SLC19A2 (HGNC:10938): (solute carrier family 19 member 2) This gene encodes the thiamin transporter protein. Mutations in this gene cause thiamin-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A2	NM_006996.3	c.1365+803A>G		intron_variant		ENST00000236137.10
SLC19A2	NM_001319667.1	c.762+803A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A2	ENST00000236137.10	c.1365+803A>G		intron_variant		1	NM_006996.3	P1
SLC19A2	ENST00000367804.4	c.762+803A>G		intron_variant		1
SLC19A2	ENST00000646596.1	c.1266+803A>G		intron_variant
SLC19A2	ENST00000643377.1	n.1087+803A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110149 AN: 151990 Hom.: 40087 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.725 AC: 110274 AN: 152108 Hom.: 40149 Cov.: 32 AF XY: 0.728 AC XY: 54140 AN XY: 74336

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.813

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.732

Alfa AF: 0.720 Hom.: 52088

Bravo AF: 0.730

Asia WGS AF: 0.799 AC: 2781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.051
Dann	Benign	0.45

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: rs6656822; hg19: chr1-169436546;