4-140562581-A-C

Variant names:

• chr4-140562581-A-C
• rs1494808
• NM_021833.5:c.629-208T>G

Variant summary

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

The NM_021833.5(UCP1):​c.629-208T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,030 control chromosomes in the GnomAD database, including 16,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (16969 hom., cov: 32)
• Consequence: UCP1 NM_021833.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.232

Genes affected

UCP1 (HGNC:12517): (uncoupling protein 1) Mitochondrial uncoupling proteins (UCP) are members of the family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. This gene is expressed only in brown adipose tissue, a specialized tissue which functions to produce heat. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 4-140562581-A-C is Benign according to our data. Variant chr4-140562581-A-C is described in ClinVar as [Benign]. Clinvar id is 1267017.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UCP1	NM_021833.5	c.629-208T>G		intron_variant	Intron 4 of 5	ENST00000262999.4	NP_068605.1
UCP1	XM_005263206.4	c.626-208T>G		intron_variant	Intron 4 of 5		XP_005263263.1
UCP1	XM_011532228.3	c.629-208T>G		intron_variant	Intron 4 of 5		XP_011530530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UCP1	ENST00000262999.4	c.629-208T>G		intron_variant	Intron 4 of 5	1	NM_021833.5	ENSP00000262999.3

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67446 AN: 151912 Hom.: 16938 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.444 AC: 67532 AN: 152030 Hom.: 16969 Cov.: 32 AF XY: 0.448 AC XY: 33321 AN XY: 74328

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.427

Alfa AF: 0.388 Hom.: 1630

Bravo AF: 0.462

Asia WGS AF: 0.518 AC: 1802 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.78

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: rs1494808; hg19: chr4-141483735;