Genetic Variant ANGPTL6:c.-11+90C>T (chr19-10102478-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_031917.3(ANGPTL6):c.-11+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.096 in 819,958 control chromosomes in the GnomAD database, including 4,523 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 0.079 ( 683 hom., cov: 31)

Exomes 𝑓: 0.10 ( 3840 hom. )

Consequence

ANGPTL6
NM_031917.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

22 publications found

Variant links:

Genes affected

ANGPTL6 (HGNC:23140): (angiopoietin like 6) Predicted to enable signaling receptor binding activity. Predicted to be involved in angiogenesis and cell differentiation. Located in extracellular exosome. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ANGPTL6 Gene-Disease associations (from GenCC):

intracranial berry aneurysm
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANGPTL6 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL6	NM_031917.3 link	c.-11+90C>T		intron_variant	Intron 1 of 5	ENST00000253109.5	NP_114123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPTL6	ENST00000253109.5 link	c.-11+90C>T		intron_variant	Intron 1 of 5	1	NM_031917.3	ENSP00000253109.3
ANGPTL6	ENST00000592641.5 link	c.-11+74C>T		intron_variant	Intron 1 of 5	1		ENSP00000467930.1

Frequencies

GnomAD3 genomes

AF:

0.0790

AC:

11953

AN:

151394

Hom.:

683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0582

Gnomad ASJ

AF:

0.0580

Gnomad EAS

AF:

0.000967

Gnomad SAS

AF:

0.0414

Gnomad FIN

AF:

0.0860

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0641

GnomAD4 exome

AF:

0.0998

AC:

66728

AN:

668446

Hom.:

3840

AF XY:

0.0991

AC XY:

30842

AN XY:

311164

show subpopulations

African (AFR)

AF:

0.0550

AC:

697

AN:

12672

American (AMR)

AF:

0.0510

AC:

AN:

764

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

298

AN:

4274

East Asian (EAS)

AF:

0.000337

AC:

AN:

2968

South Asian (SAS)

AF:

0.0480

AC:

647

AN:

13490

European-Finnish (FIN)

AF:

0.0955

AC:

AN:

220

Middle Eastern (MID)

AF:

0.0659

AC:

AN:

1350

European-Non Finnish (NFE)

AF:

0.103

AC:

63010

AN:

610640

Other (OTH)

AF:

0.0873

AC:

1926

AN:

22068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2698

5395

8093

10790

13488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3084

6168

9252

12336

15420

<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:

0.0789

AC:

11958

AN:

151512

Hom.:

683

Cov.:

AF XY:

0.0764

AC XY:

5651

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.0565

AC:

2344

AN:

41460

American (AMR)

AF:

0.0581

AC:

885

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.0580

AC:

201

AN:

3468

East Asian (EAS)

AF:

0.000970

AC:

AN:

5156

South Asian (SAS)

AF:

0.0419

AC:

202

AN:

4824

European-Finnish (FIN)

AF:

0.0860

AC:

897

AN:

10430

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7181

AN:

67648

Other (OTH)

AF:

0.0635

AC:

133

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

494

988

1483

1977

2471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0893

Hom.:

1546

Bravo

AF:

0.0745

Asia WGS

AF:

0.0210

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

(source)

DANN

Benign

0.64

PhyloP100

0.085

PromoterAI

0.067

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over