rs3765227

Positions:

• chr1-169467915-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006996.3(SLC19A2):​c.1365+196G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 152,248 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.041 (196 hom., cov: 32)
• Consequence: SLC19A2 NM_006996.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.179

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]

SLC19A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-169467915-C-A is Benign according to our data. Variant chr1-169467915-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 673628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A2	NM_006996.3	c.1365+196G>T		intron_variant		ENST00000236137.10	NP_008927.1
SLC19A2	NM_001319667.1	c.762+196G>T		intron_variant			NP_001306596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A2	ENST00000236137.10	c.1365+196G>T		intron_variant		1	NM_006996.3	ENSP00000236137.5
SLC19A2	ENST00000367804.4	c.762+196G>T		intron_variant		1		ENSP00000356778.3
SLC19A2	ENST00000646596.1	c.1266+196G>T		intron_variant				ENSP00000494404.1
SLC19A2	ENST00000643377.1	n.1087+196G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6300 AN: 152130 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.00481

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0414 AC: 6304 AN: 152248 Hom.: 196 Cov.: 32 AF XY: 0.0412 AC XY: 3068 AN XY: 74446

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.0442

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0791

Gnomad4 FIN AF: 0.00481

Gnomad4 NFE AF: 0.0428

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0367 Hom.: 8

Bravo AF: 0.0433

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3765227; hg19: chr1-169437153;