Genetic Variant NM_015305.4:c.*1472C>T (chr14-76787756-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_015305.4(ANGEL1):c.*1472C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,518 control chromosomes in the GnomAD database, including 983 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 0.11 ( 982 hom., cov: 32)

Exomes 𝑓: 0.12 ( 1 hom. )

Consequence

ANGEL1
NM_015305.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.496

Publications

11 publications found

Variant links:

Genes affected

ANGEL1 (HGNC:19961): (angel homolog 1) Enables eukaryotic initiation factor 4E binding activity and protein domain specific binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, exonucleolytic. Located in several cellular components, including cis-Golgi network; endoplasmic reticulum; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ANGEL1 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015305.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGEL1	NM_015305.4	MANE Select	c.*1472C>T	3_prime_UTR	Exon 10 of 10	NP_056120.2	Q9UNK9
ANGEL1	NM_001370747.1		c.*1472C>T	3_prime_UTR	Exon 12 of 12	NP_001357676.1
ANGEL1	NM_001370746.1		c.2012-1164C>T	intron	N/A	NP_001357675.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGEL1	ENST00000251089.8	TSL:1 MANE Select	c.*1472C>T	3_prime_UTR	Exon 10 of 10	ENSP00000251089.3	Q9UNK9
ANGEL1	ENST00000851327.1		c.*1472C>T	3_prime_UTR	Exon 12 of 12	ENSP00000521386.1
ANGEL1	ENST00000557497.2	TSL:2	c.*1472C>T	3_prime_UTR	Exon 11 of 11	ENSP00000498076.2	A0A3B3IU54

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16268

AN:

152086

Hom.:

984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0944

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0704

Gnomad ASJ

AF:

0.0677

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0938

GnomAD4 exome

AF:

0.124

AC:

AN:

314

Hom.:

Cov.:

AF XY:

0.117

AC XY:

AN XY:

196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.142

AC:

AN:

268

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.107

AC:

16280

AN:

152204

Hom.:

982

Cov.:

AF XY:

0.111

AC XY:

8268

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0945

AC:

3924

AN:

41532

American (AMR)

AF:

0.0702

AC:

1074

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0677

AC:

235

AN:

3472

East Asian (EAS)

AF:

0.250

AC:

1292

AN:

5168

South Asian (SAS)

AF:

0.100

AC:

484

AN:

4826

European-Finnish (FIN)

AF:

0.174

AC:

1846

AN:

10594

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7151

AN:

67994

Other (OTH)

AF:

0.0938

AC:

198

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

731

1462

2194

2925

3656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0884

Hom.:

440

Bravo

AF:

0.101

Asia WGS

AF:

0.157

AC:

544

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.72

(source)

DANN

Benign

0.36

PhyloP100

-0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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