4-140565830-C-T

Position:

• chr4-140565830-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021833.5(UCP1):​c.325+1949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,048 control chromosomes in the GnomAD database, including 3,185 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3185 hom., cov: 32)
• Consequence: UCP1 NM_021833.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UCP1	NM_021833.5	c.325+1949G>A		intron_variant		ENST00000262999.4	NP_068605.1
UCP1	XM_005263206.4	c.325+1949G>A		intron_variant			XP_005263263.1
UCP1	XM_011532228.3	c.325+1949G>A		intron_variant			XP_011530530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UCP1	ENST00000262999.4	c.325+1949G>A		intron_variant		1	NM_021833.5	ENSP00000262999.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30471 AN: 151930 Hom.: 3184 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.201 AC: 30496 AN: 152048 Hom.: 3185 Cov.: 32 AF XY: 0.201 AC XY: 14934 AN XY: 74318

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.201

Alfa AF: 0.192 Hom.: 538

Bravo AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.8
DANN	Benign	0.68

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: rs1430583; hg19: chr4-141486984;