rs7003945

Positions:

• chr8-144326802-G-A
• chr8-144326802-G-C

Variant summary

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

The NM_012079.6(DGAT1):​c.-166C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 434,950 control chromosomes in the GnomAD database, including 47,421 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 0.39 (13318 hom., cov: 34)
  • Exomes 𝑓: 0.49 (34103 hom.)
• Consequence: DGAT1 NM_012079.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.69

Genes affected

DGAT1 (HGNC:2843): (diacylglycerol O-acyltransferase 1) This gene encodes an multipass transmembrane protein that functions as a key metabolic enzyme. The encoded protein catalyzes the conversion of diacylglycerol and fatty acyl CoA to triacylglycerol. This enzyme can also transfer acyl CoA to retinol. Activity of this protein may be associated with obesity and other metabolic diseases. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGAT1	NM_012079.6	c.-166C>T		5_prime_UTR_premature_start_codon_gain_variant	1/17	ENST00000528718.6	NP_036211.2
DGAT1	NM_012079.6	c.-166C>T		5_prime_UTR_variant	1/17	ENST00000528718.6	NP_036211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGAT1	ENST00000528718.6	c.-166C>T		5_prime_UTR_premature_start_codon_gain_variant	1/17	1	NM_012079.6	ENSP00000482264.1
DGAT1	ENST00000528718.6	c.-166C>T		5_prime_UTR_variant	1/17	1	NM_012079.6	ENSP00000482264.1
DGAT1	ENST00000332324.5	c.-166C>T		5_prime_UTR_premature_start_codon_gain_variant	1/10	5		ENSP00000332258.5
DGAT1	ENST00000332324.5	c.-166C>T		5_prime_UTR_variant	1/10	5		ENSP00000332258.5

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59767 AN: 151966 Hom.: 13318 Cov.: 34

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.485 AC: 137215 AN: 282876 Hom.: 34103 Cov.: 5 AF XY: 0.485 AC XY: 67612 AN XY: 139280

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.344

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.393 AC: 59766 AN: 152074 Hom.: 13318 Cov.: 34 AF XY: 0.389 AC XY: 28922 AN XY: 74352

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.400

Alfa AF: 0.302 Hom.: 855

Bravo AF: 0.372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7003945; hg19: chr8-145550465;