rs56180335

chr8-144318358-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012079.6(DGAT1):c.579C>T(p.Gly193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,610,914 control chromosomes in the GnomAD database, including 3,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (232 hom., cov: 33)
  • Exomes 𝑓: 0.065 (3434 hom.)
• Consequence: DGAT1 NM_012079.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.158

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 8-144318358-G-A is Benign according to our data. Variant chr8-144318358-G-A is described in ClinVar as [Benign]. Clinvar id is 402588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.158 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGAT1	NM_012079.6	c.579C>T	p.Gly193=	synonymous_variant	7/17	ENST00000528718.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGAT1	ENST00000528718.6	c.579C>T	p.Gly193=	synonymous_variant	7/17	1	NM_012079.6	P1

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 7034 AN: 152204 Hom.: 232 Cov.: 33

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0397

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0105

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0669

GnomAD3 exomes AF: 0.0474 AC: 11711 AN: 246882 Hom.: 382 AF XY: 0.0482 AC XY: 6465 AN XY: 134132

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.0371

Gnomad ASJ exome AF: 0.0457

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.0128

Gnomad FIN exome AF: 0.0460

Gnomad NFE exome AF: 0.0733

Gnomad OTH exome AF: 0.0535

GnomAD4 exome AF: 0.0649 AC: 94590 AN: 1458592 Hom.: 3434 Cov.: 34 AF XY: 0.0636 AC XY: 46112 AN XY: 725412

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0387

Gnomad4 ASJ exome AF: 0.0448

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.0469

Gnomad4 NFE exome AF: 0.0757

Gnomad4 OTH exome AF: 0.0577

GnomAD4 genome AF: 0.0462 AC: 7032 AN: 152322 Hom.: 232 Cov.: 33 AF XY: 0.0442 AC XY: 3293 AN XY: 74478

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0500

Gnomad4 ASJ AF: 0.0397

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.0616 Hom.: 197

Bravo AF: 0.0459

Asia WGS AF: 0.00606 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	7.4
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs56180335; hg19: chr8-145542021;