rs55907012

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 13/21 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.37

Publications

7 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

congenital diarrhea 7 with exudative enteropathy
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

DGAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 402589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012079.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT1	NM_012079.6	MANE Select	c.455A>G	p.Lys152Arg	missense	Exon 5 of 17	NP_036211.2	O75907

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGAT1	ENST00000528718.6	TSL:1 MANE Select	c.455A>G	p.Lys152Arg	missense	Exon 5 of 17	ENSP00000482264.1	O75907
DGAT1	ENST00000875296.1		c.455A>G	p.Lys152Arg	missense	Exon 5 of 17	ENSP00000545355.1
DGAT1	ENST00000875297.1		c.455A>G	p.Lys152Arg	missense	Exon 5 of 17	ENSP00000545356.1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1965

AN:

152190

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0137

AC:

3257

AN:

238336

AF XY:

0.0141

show subpopulations

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 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.:

AF XY:

0.0169

AC XY:

12249

AN XY:

723992

show subpopulations

African (AFR)

AF:

0.00272

AC:

AN:

33434

American (AMR)

AF:

0.0127

AC:

557

AN:

43766

Ashkenazi Jewish (ASJ)

AF:

0.0434

AC:

1125

AN:

25900

East Asian (EAS)

AF:

0.000101

AC:

AN:

39524

South Asian (SAS)

AF:

0.00585

AC:

499

AN:

85326

European-Finnish (FIN)

AF:

0.00407

AC:

214

AN:

52536

Middle Eastern (MID)

AF:

0.0168

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0192

AC:

21286

AN:

1109966

Other (OTH)

AF:

0.0190

AC:

1146

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

1598

3196

4794

6392

7990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

804

1608

2412

3216

4020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0129

AC:

1964

AN:

152308

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

861

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00298

AC:

124

AN:

41568

American (AMR)

AF:

0.0162

AC:

248

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.00394

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00386

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0195

AC:

1327

AN:

68016

Other (OTH)

AF:

0.0170

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

195

292

390

487

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0174

Hom.:

Bravo

AF:

0.0133

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0219

AC:

188

ExAC

AF:

0.0133

AC:

1609

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.31

MetaRNN

Benign

0.0042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.060

PhyloP100

1.4

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.86

REVEL

Benign

0.043

Sift

Benign

0.28

Sift4G

Benign

0.82

Polyphen

0.011

Vest4

0.20

MPC

0.22

ClinPred

0.0051

GERP RS

2.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.13

gMVP

0.25

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over