Genetic Variant DGAT1:c.-39G>A (chr8-144326675-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_012079.6(DGAT1):c.-39G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,160,616 control chromosomes in the GnomAD database, including 10,089 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1159 hom., cov: 33)

Exomes 𝑓: 0.13 ( 8930 hom. )

Consequence

DGAT1
NM_012079.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.713

Publications

8 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

DGAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGAT1	NM_012079.6	MANE Select	c.-39G>A		5_prime_UTR	Exon 1 of 17	NP_036211.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DGAT1	ENST00000528718.6	TSL:1 MANE Select	c.-39G>A	5_prime_UTR	Exon 1 of 17	ENSP00000482264.1
DGAT1	ENST00000332324.5	TSL:5	c.-39G>A	5_prime_UTR	Exon 1 of 10	ENSP00000332258.5
DGAT1	ENST00000525371.1	TSL:5	n.-8G>A	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17725

AN:

151728

Hom.:

1160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.0687

Gnomad ASJ

AF:

0.0979

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0614

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.129

AC:

130065

AN:

1008780

Hom.:

8930

Cov.:

AF XY:

0.129

AC XY:

61719

AN XY:

479026

show subpopulations

African (AFR)

AF:

0.120

AC:

2383

AN:

19778

American (AMR)

AF:

0.0606

AC:

362

AN:

5970

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

1144

AN:

10614

East Asian (EAS)

AF:

0.000966

AC:

AN:

16562

South Asian (SAS)

AF:

0.0760

AC:

1838

AN:

24176

European-Finnish (FIN)

AF:

0.181

AC:

3110

AN:

17206

Middle Eastern (MID)

AF:

0.0924

AC:

227

AN:

2458

European-Non Finnish (NFE)

AF:

0.133

AC:

116531

AN:

874346

Other (OTH)

AF:

0.118

AC:

4454

AN:

37670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

5941

11882

17822

23763

29704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4968

9936

14904

19872

24840

<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:

0.117

AC:

17733

AN:

151836

Hom.:

1159

Cov.:

AF XY:

0.116

AC XY:

8584

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.117

AC:

4858

AN:

41472

American (AMR)

AF:

0.0684

AC:

1044

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0979

AC:

339

AN:

3464

East Asian (EAS)

AF:

0.00174

AC:

AN:

5176

South Asian (SAS)

AF:

0.0617

AC:

298

AN:

4830

European-Finnish (FIN)

AF:

0.165

AC:

1715

AN:

10410

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.133

AC:

9062

AN:

67926

Other (OTH)

AF:

0.109

AC:

229

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

811

1622

2433

3244

4055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0802

Hom.:

109

Bravo

AF:

0.107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

PhyloP100

-0.71

PromoterAI

0.16

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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