8-144316614-G-A

Position:

• chr8-144316614-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_012079.6(DGAT1):​c.1407C>T​(p.Val469Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,608,286 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: DGAT1 NM_012079.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.657

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]

DGAT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008397639).
• BP6: Variant 8-144316614-G-A is Benign according to our data. Variant chr8-144316614-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 722323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144316614-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.657 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGAT1	NM_012079.6	c.1407C>T	p.Val469Val	synonymous_variant	17/17	ENST00000528718.6	NP_036211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGAT1	ENST00000528718.6	c.1407C>T	p.Val469Val	synonymous_variant	17/17	1	NM_012079.6	ENSP00000482264.1
DGAT1	ENST00000332324.5	c.910C>T	p.Pro304Ser	missense_variant	10/10	5		ENSP00000332258.5
DGAT1	ENST00000524965.5	n.1042C>T		non_coding_transcript_exon_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152236 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00113 AC: 269 AN: 238828 Hom.: 0 AF XY: 0.00122 AC XY: 158 AN XY: 129526

Gnomad AFR exome AF: 0.000268

Gnomad AMR exome AF: 0.000627

Gnomad ASJ exome AF: 0.00817

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000841

Gnomad NFE exome AF: 0.00133

Gnomad OTH exome AF: 0.000683

GnomAD4 exome AF: 0.00170 AC: 2482 AN: 1455932 Hom.: 4 Cov.: 33 AF XY: 0.00169 AC XY: 1225 AN XY: 723724

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000500

Gnomad4 ASJ exome AF: 0.00811

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000980

Gnomad4 NFE exome AF: 0.00189

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152354 Hom.: 1 Cov.: 33 AF XY: 0.00117 AC XY: 87 AN XY: 74502

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00197

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00212 Hom.: 0

Bravo AF: 0.00118

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00102 AC: 123

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	DGAT1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

DGAT1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 04, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.5
DANN	Uncertain	0.98
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.88	D
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	1.0	D;N
Sift4G	Pathogenic	0.0	D
Vest4		0.16
MVP		0.37
ClinPred		0.0029	T
GERP RS		1.6

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: rs17851331; hg19: chr8-145540277;