dbSNP rs15723: ANGPTL6:c.*94T>C (chr19-10092495-A-G) – 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.*94T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 1,523,504 control chromosomes in the GnomAD database, including 6,462 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 0.072 ( 476 hom., cov: 32)

Exomes 𝑓: 0.089 ( 5986 hom. )

Consequence

ANGPTL6
NM_031917.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.397

Publications

17 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 links:

SHFL (HGNC:25649): (shiftless antiviral inhibitor of ribosomal frameshifting) This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

SHFL 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL6	NM_031917.3 link	c.*94T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000253109.5	NP_114123.2
SHFL	NM_018381.4 link	c.*193A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000253110.16	NP_060851.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPTL6	ENST00000253109.5 link	c.*94T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_031917.3	ENSP00000253109.3
SHFL	ENST00000253110.16 link	c.*193A>G		3_prime_UTR_variant	Exon 8 of 8	2	NM_018381.4	ENSP00000253110.10

Frequencies

GnomAD3 genomes

AF:

0.0722

AC:

10979

AN:

152122

Hom.:

476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0374

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.0564

Gnomad ASJ

AF:

0.0634

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0435

Gnomad FIN

AF:

0.0844

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0583

GnomAD4 exome

AF:

0.0891

AC:

122122

AN:

1371264

Hom.:

5986

Cov.:

AF XY:

0.0878

AC XY:

59312

AN XY:

675456

show subpopulations

African (AFR)

AF:

0.0366

AC:

1126

AN:

30776

American (AMR)

AF:

0.0394

AC:

1346

AN:

34182

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

1506

AN:

21600

East Asian (EAS)

AF:

0.000308

AC:

AN:

38980

South Asian (SAS)

AF:

0.0481

AC:

3547

AN:

73742

European-Finnish (FIN)

AF:

0.0825

AC:

4114

AN:

49884

Middle Eastern (MID)

AF:

0.0771

AC:

377

AN:

4890

European-Non Finnish (NFE)

AF:

0.0997

AC:

105720

AN:

1060498

Other (OTH)

AF:

0.0771

AC:

4374

AN:

56712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

5708

11417

17125

22834

28542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3810

7620

11430

15240

19050

<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:

0.0722

AC:

10986

AN:

152240

Hom.:

476

Cov.:

AF XY:

0.0703

AC XY:

5233

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0373

AC:

1551

AN:

41546

American (AMR)

AF:

0.0564

AC:

862

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0634

AC:

220

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0441

AC:

213

AN:

4828

European-Finnish (FIN)

AF:

0.0844

AC:

896

AN:

10612

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7014

AN:

67988

Other (OTH)

AF:

0.0577

AC:

122

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

506

1013

1519

2026

2532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0888

Hom.:

1356

Bravo

AF:

0.0670

Asia WGS

AF:

0.0220

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.63

(source)

DANN

Benign

0.45

PhyloP100

-0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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