dbSNP rs8109578: 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031917.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGPTL6	NM_031917.3	MANE Select	c.-11+90C>T	intron	N/A	NP_114123.2
ANGPTL6	NM_001321411.2		c.-11+74C>T	intron	N/A	NP_001308340.1	Q8NI99
ANGPTL6	NM_001387347.1		c.-11+90C>T	intron	N/A	NP_001374276.1	Q8NI99

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGPTL6	ENST00000253109.5	TSL:1 MANE Select	c.-11+90C>T	intron	N/A	ENSP00000253109.3	Q8NI99
ANGPTL6	ENST00000592641.5	TSL:1	c.-11+74C>T	intron	N/A	ENSP00000467930.1	Q8NI99
ANGPTL6	ENST00000890998.1		c.-11+90C>T	intron	N/A	ENSP00000561057.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over