8-144318712-T-C

Position:

• chr8-144318712-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012079.6(DGAT1):​c.455A>G​(p.Lys152Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,608,698 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (26 hom., cov: 33)
  • Exomes 𝑓: 0.017 (260 hom.)
• Consequence: DGAT1 NM_012079.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.37

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041535497).
• BP6: Variant 8-144318712-T-C is Benign according to our data. Variant chr8-144318712-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 402589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144318712-T-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1964/152308) while in subpopulation NFE AF= 0.0195 (1327/68016). AF 95% confidence interval is 0.0186. There are 26 homozygotes in gnomad4. There are 861 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGAT1	NM_012079.6	c.455A>G	p.Lys152Arg	missense_variant	5/17	ENST00000528718.6	NP_036211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGAT1	ENST00000528718.6	c.455A>G	p.Lys152Arg	missense_variant	5/17	1	NM_012079.6	ENSP00000482264	P1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1965 AN: 152190 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00386

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0137 AC: 3257 AN: 238336 Hom.: 36 AF XY: 0.0141 AC XY: 1822 AN XY: 129294

Gnomad AFR exome AF: 0.00302

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.0416

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00613

Gnomad FIN exome AF: 0.00370

Gnomad NFE exome AF: 0.0192

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0172 AC: 25019 AN: 1456390 Hom.: 260 Cov.: 37 AF XY: 0.0169 AC XY: 12249 AN XY: 723992

Gnomad4 AFR exome AF: 0.00272

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.0434

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00585

Gnomad4 FIN exome AF: 0.00407

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0190

GnomAD4 genome AF: 0.0129 AC: 1964 AN: 152308 Hom.: 26 Cov.: 33 AF XY: 0.0116 AC XY: 861 AN XY: 74472

Gnomad4 AFR AF: 0.00298

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00386

Gnomad4 NFE AF: 0.0195

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0184 Hom.: 33

Bravo AF: 0.0133

TwinsUK AF: 0.0181 AC: 67

ALSPAC AF: 0.0135 AC: 52

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0219 AC: 188

ExAC AF: 0.0133 AC: 1609

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified Benign:1

Likely 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: 1.6% of total chromosomes in ExAC, 2.4% European chromosomes -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.31	N
MetaRNN	Benign	0.0042	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.060	N;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.86	.;N
REVEL	Benign	0.043
Sift	Benign	0.28	.;T
Sift4G	Benign	0.82	T;T
Polyphen		0.011	B;.
Vest4		0.20
MPC		0.22
ClinPred		0.0051	T
GERP RS		2.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.13
gMVP		0.25

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: rs55907012; hg19: chr8-145542375;