dbSNP rs7003945: DGAT1:c.-166C>T (chr8-144326802-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012079.6(DGAT1):c.-166C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 434,950 control chromosomes in the GnomAD database, including 47,421 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 0.39 ( 13318 hom., cov: 34)

Exomes 𝑓: 0.49 ( 34103 hom. )

Consequence

DGAT1
NM_012079.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.69

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGAT1	NM_012079.6 link	c.-166C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	ENST00000528718.6	NP_036211.2	O75907
DGAT1	NM_012079.6 link	c.-166C>T		5_prime_UTR_variant	Exon 1 of 17	ENST00000528718.6	NP_036211.2	O75907

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGAT1	ENST00000528718.6 link	c.-166C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	1	NM_012079.6	ENSP00000482264.1		O75907
DGAT1	ENST00000528718.6 link	c.-166C>T		5_prime_UTR_variant	Exon 1 of 17	1	NM_012079.6	ENSP00000482264.1		O75907

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59767

AN:

151966

Hom.:

13318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.189

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.513

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.399

GnomAD4 exome

AF:

0.485

AC:

137215

AN:

282876

Hom.:

34103

Cov.:

AF XY:

0.485

AC XY:

67612

AN XY:

139280

show subpopulations

African (AFR)

AF:

0.162

AC:

942

AN:

5826

American (AMR)

AF:

0.306

AC:

855

AN:

2792

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1887

AN:

3686

East Asian (EAS)

AF:

0.482

AC:

3053

AN:

6328

South Asian (SAS)

AF:

0.344

AC:

1716

AN:

4992

European-Finnish (FIN)

AF:

0.471

AC:

4557

AN:

9678

Middle Eastern (MID)

AF:

0.427

AC:

341

AN:

798

European-Non Finnish (NFE)

AF:

0.500

AC:

118413

AN:

236794

Other (OTH)

AF:

0.455

AC:

5451

AN:

11982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

3417

6833

10250

13666

17083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3640

7280

10920

14560

18200

<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:

0.393

AC:

59766

AN:

152074

Hom.:

13318

Cov.:

AF XY:

0.389

AC XY:

28922

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.188

AC:

7816

AN:

41522

American (AMR)

AF:

0.324

AC:

4952

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

1778

AN:

3468

East Asian (EAS)

AF:

0.522

AC:

2693

AN:

5156

South Asian (SAS)

AF:

0.347

AC:

1675

AN:

4828

European-Finnish (FIN)

AF:

0.458

AC:

4839

AN:

10554

Middle Eastern (MID)

AF:

0.452

AC:

132

AN:

292

European-Non Finnish (NFE)

AF:

0.507

AC:

34425

AN:

67946

Other (OTH)

AF:

0.400

AC:

842

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1740

3480

5219

6959

8699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.302

Hom.:

855

Bravo

AF:

0.372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.92

(source)

PhyloP100

-5.7

PromoterAI

0.044

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over