dbSNP rs4646298: MIR3936HG:n.73+317G>A (chr5-132369527-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000457998.2(MIR3936HG):n.122G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 162,174 control chromosomes in the GnomAD database, including 616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.076 ( 569 hom., cov: 32)

Exomes 𝑓: 0.079 ( 47 hom. )

Consequence

MIR3936HG
ENST00000457998.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.94

Variant links:

Genes affected

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

MIR3936HG links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-132369527-C-T is Benign according to our data. Variant chr5-132369527-C-T is described in ClinVar as [Benign]. Clinvar id is 1236418.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A5	NM_003060.4 link	c.-446C>T		upstream_gene_variant		ENST00000245407.8	NP_003051.1	O76082-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A5	ENST00000245407.8 link	c.-446C>T		upstream_gene_variant		1	NM_003060.4	ENSP00000245407.3		O76082-1

Frequencies

GnomAD3 genomes

AF:

0.0764

AC:

11621

AN:

152038

Hom.:

572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0492

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.0651

Gnomad FIN

AF:

0.0733

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0764

Gnomad OTH

AF:

0.0762

GnomAD4 exome

AF:

0.0792

AC:

793

AN:

10018

Hom.:

Cov.:

AF XY:

0.0771

AC XY:

399

AN XY:

5178

show subpopulations

Gnomad4 AFR exome

AF:

0.0698

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.0820

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.0612

Gnomad4 FIN exome

AF:

0.0597

Gnomad4 NFE exome

AF:

0.0684

Gnomad4 OTH exome

AF:

0.102

GnomAD4 genome

AF:

0.0764

AC:

11621

AN:

152156

Hom.:

569

Cov.:

AF XY:

0.0755

AC XY:

5617

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0616

Gnomad4 AMR

AF:

0.0491

Gnomad4 ASJ

AF:

0.109

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.0650

Gnomad4 FIN

AF:

0.0733

Gnomad4 NFE

AF:

0.0764

Gnomad4 OTH

AF:

0.0764

Alfa

AF:

0.0769

Hom.:

Bravo

AF:

0.0745

Asia WGS

AF:

0.123

AC:

429

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.19

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over