rs274549

Variant names:

• chr5-132393426-A-C
• rs274549
• NM_003060.4:c.1451-250A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132393426-A-C
• chr5-132393426-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003060.4(SLC22A5):​c.1451-250A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,076 control chromosomes in the GnomAD database, including 45,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (45027 hom., cov: 31)
• Consequence: SLC22A5 NM_003060.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.651
• Publications: 16 publications found

Genes affected

SLC22A5 (HGNC:10969): (solute carrier family 22 member 5) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SLC22A5 Gene-Disease associations (from GenCC):

• systemic primary carnitine deficiency disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
• short QT syndrome

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-132393426-A-C is Benign according to our data. Variant chr5-132393426-A-C is described in ClinVar as Benign. ClinVar VariationId is 670107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4	c.1451-250A>C		intron_variant	Intron 8 of 9	ENST00000245407.8	NP_003051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8	c.1451-250A>C		intron_variant	Intron 8 of 9	1	NM_003060.4	ENSP00000245407.3

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114791 AN: 151958 Hom.: 45029 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.755 AC: 114821 AN: 152076 Hom.: 45027 Cov.: 31 AF XY: 0.759 AC XY: 56402 AN XY: 74326

African (AFR) AF: 0.519 AC: 21503 AN: 41450

American (AMR) AF: 0.811 AC: 12397 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3015 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4715 AN: 5176

South Asian (SAS) AF: 0.832 AC: 4009 AN: 4818

European-Finnish (FIN) AF: 0.869 AC: 9202 AN: 10586

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57326 AN: 67966

Other (OTH) AF: 0.785 AC: 1662 AN: 2116

Alfa AF: 0.814 Hom.: 86054

Bravo AF: 0.742

Asia WGS AF: 0.805 AC: 2797 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.90
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.65
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: rs274549; hg19: chr5-131729118;