rs2631367

Variant names:

• chr5-132369766-C-G
• rs2631367
• NM_003060.4:c.-207C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-132369766-C-G
• chr5-132369766-C-A
• chr5-132369766-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003060.4(SLC22A5):​c.-207C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 592,348 control chromosomes in the GnomAD database, including 110,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27799 hom., cov: 33)
  • Exomes 𝑓: 0.60 (82696 hom.)
• Consequence: SLC22A5 NM_003060.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.35
• Publications: 107 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]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-132369766-C-G is Benign according to our data. Variant chr5-132369766-C-G is described in ClinVar as Benign. ClinVar VariationId is 350806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003060.4. 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
	SLC22A5	NM_003060.4	MANE Select	c.-207C>G		5_prime_UTR	Exon 1 of 10	NP_003051.1	O76082-1
	SLC22A5	NM_001308122.2		c.-207C>G		5_prime_UTR	Exon 1 of 11	NP_001295051.1	O76082-3
	MIR3936HG	NR_110997.1		n.73+78G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A5	ENST00000245407.8	TSL:1 MANE Select	c.-207C>G		5_prime_UTR	Exon 1 of 10	ENSP00000245407.3	O76082-1
	MIR3936HG	ENST00000621103.4	TSL:1	n.73+78G>C		intron	N/A
	SLC22A5	ENST00000893299.1		c.-207C>G		5_prime_UTR	Exon 1 of 10	ENSP00000563358.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90534 AN: 151872 Hom.: 27771 Cov.: 33

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.596 AC: 262284 AN: 440368 Hom.: 82696 Cov.: 6 AF XY: 0.605 AC XY: 138440 AN XY: 228810

African (AFR) AF: 0.607 AC: 5312 AN: 8746

American (AMR) AF: 0.673 AC: 6432 AN: 9564

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 5591 AN: 11622

East Asian (EAS) AF: 0.999 AC: 25012 AN: 25036

South Asian (SAS) AF: 0.857 AC: 29454 AN: 34372

European-Finnish (FIN) AF: 0.662 AC: 18780 AN: 28356

Middle Eastern (MID) AF: 0.568 AC: 1055 AN: 1858

European-Non Finnish (NFE) AF: 0.528 AC: 156492 AN: 296430

Other (OTH) AF: 0.581 AC: 14156 AN: 24384

GnomAD4 genome AF: 0.596 AC: 90608 AN: 151980 Hom.: 27799 Cov.: 33 AF XY: 0.610 AC XY: 45362 AN XY: 74306

African (AFR) AF: 0.605 AC: 25094 AN: 41472

American (AMR) AF: 0.615 AC: 9402 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1716 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5129 AN: 5144

South Asian (SAS) AF: 0.872 AC: 4213 AN: 4832

European-Finnish (FIN) AF: 0.665 AC: 7015 AN: 10546

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36398 AN: 67926

Other (OTH) AF: 0.559 AC: 1179 AN: 2108

Alfa AF: 0.581 Hom.: 3213

Bravo AF: 0.587

Asia WGS AF: 0.908 AC: 3144 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Renal carnitine transport defect (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		1.3
PromoterAI		0.55	Over-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs2631367; hg19: chr5-131705458;