rs17518769

chr1-169482852-G-A

Variant summary

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

The NM_006996.3(SLC19A2):c.204+2711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,030 control chromosomes in the GnomAD database, including 1,812 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 0.13 (1812 hom., cov: 32)
• Consequence: SLC19A2 NM_006996.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A2	NM_006996.3	c.204+2711C>T		intron_variant		ENST00000236137.10
SLC19A2	NM_001319667.1	c.204+2711C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A2	ENST00000236137.10	c.204+2711C>T		intron_variant		1	NM_006996.3	P1
SLC19A2	ENST00000367804.4	c.204+2711C>T		intron_variant		1
SLC19A2	ENST00000646596.1	c.204+2711C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19877 AN: 151912 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.131 AC: 19907 AN: 152030 Hom.: 1812 Cov.: 32 AF XY: 0.128 AC XY: 9491 AN XY: 74334

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0820

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0967 Hom.: 1122

Bravo AF: 0.140

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	1.2
Dann	Benign	0.77

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: rs17518769; hg19: chr1-169452090;