chr8-144316567-G-A

Position:

• chr8-144316567-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012079.6(DGAT1):​c.1454C>T​(p.Ala485Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,596,822 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A485A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (36 hom.)
• Consequence: DGAT1 NM_012079.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.114

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002905786).
• BP6: Variant 8-144316567-G-A is Benign according to our data. Variant chr8-144316567-G-A is described in ClinVar as [Benign]. Clinvar id is 738939.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144316567-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00121 (184/152328) while in subpopulation SAS AF= 0.0186 (90/4834). AF 95% confidence interval is 0.0155. There are 2 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGAT1	NM_012079.6	c.1454C>T	p.Ala485Val	missense_variant	17/17	ENST00000528718.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGAT1	ENST00000528718.6	c.1454C>T	p.Ala485Val	missense_variant	17/17	1	NM_012079.6	P1
DGAT1	ENST00000332324.5	c.*9C>T		3_prime_UTR_variant	10/10	5
DGAT1	ENST00000524965.5	n.1089C>T		non_coding_transcript_exon_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 185 AN: 152210 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00271 AC: 604 AN: 223256 Hom.: 18 AF XY: 0.00354 AC XY: 427 AN XY: 120568

Gnomad AFR exome AF: 0.000145

Gnomad AMR exome AF: 0.000282

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000179

Gnomad SAS exome AF: 0.0189

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000603

Gnomad OTH exome AF: 0.000897

GnomAD4 exome AF: 0.00181 AC: 2615 AN: 1444494 Hom.: 36 Cov.: 33 AF XY: 0.00231 AC XY: 1655 AN XY: 716784

Gnomad4 AFR exome AF: 0.000241

Gnomad4 AMR exome AF: 0.000377

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000769

Gnomad4 SAS exome AF: 0.0176

Gnomad4 FIN exome AF: 0.0000196

Gnomad4 NFE exome AF: 0.000895

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00121 AC: 184 AN: 152328 Hom.: 2 Cov.: 33 AF XY: 0.00157 AC XY: 117 AN XY: 74486

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000680 Hom.: 0

Bravo AF: 0.000574

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.00294 AC: 355

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.1
DANN	Benign	0.78
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.30	N
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.27	T
Polyphen		0.039	B
Vest4		0.025
MVP		0.15
ClinPred		0.00076	T
GERP RS		-0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.024
gMVP		0.31

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: rs200430497; hg19: chr8-145540230;