Genetic Variant PAGR1:c.566-9C>T (chr16-29819546-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024516.4(PAGR1):c.566-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,613,926 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 156 hom. )

Consequence

PAGR1
NM_024516.4 intron

Scores

Splicing: ADA: 0.0002277

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.679

Publications

2 publications found

Variant links:

Genes affected

PAGR1 (HGNC:28707): (PAXIP1 associated glutamate rich protein 1) Enables estrogen receptor binding activity. Involved in positive regulation of cell cycle G1/S phase transition; positive regulation of intracellular estrogen receptor signaling pathway; and positive regulation of transcription by RNA polymerase II. Located in nucleus. Part of MLL3/4 complex. [provided by Alliance of Genome Resources, Apr 2022]

PAGR1 links:

MVP-DT (HGNC:56029): (MVP divergent transcript)

MVP-DT links:

ENSG00000281348 (HGNC:):

ENSG00000281348 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 16-29819546-C-T is Benign according to our data. Variant chr16-29819546-C-T is described in ClinVar as Benign. ClinVar VariationId is 716597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGR1	NM_024516.4	MANE Select	c.566-9C>T		intron	N/A	NP_078792.1	Q9BTK6
	MVP-DT	NR_186424.1		n.240G>A		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PAGR1	ENST00000320330.8	TSL:1 MANE Select	c.566-9C>T	intron	N/A	ENSP00000326519.6	Q9BTK6
MVP-DT	ENST00000569809.3	TSL:1	n.400G>A	non_coding_transcript_exon	Exon 2 of 3
ENSG00000281348	ENST00000562285.1	TSL:2	n.53-9C>T	intron	N/A	ENSP00000457363.1	H3BTX0

Frequencies

GnomAD3 genomes

AF:

0.00567

AC:

863

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0767

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00950

AC:

2384

AN:

251070

AF XY:

0.00869

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0801

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00816

GnomAD4 exome

AF:

0.00386

AC:

5644

AN:

1461648

Hom.:

156

Cov.:

AF XY:

0.00380

AC XY:

2763

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33480

American (AMR)

AF:

0.00125

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0776

AC:

3082

AN:

39692

South Asian (SAS)

AF:

0.00112

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0298

AC:

1588

AN:

53272

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000371

AC:

412

AN:

1111946

Other (OTH)

AF:

0.00646

AC:

390

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

314

627

941

1254

1568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.00565

AC:

860

AN:

152278

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

537

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.000914

AC:

AN:

41560

American (AMR)

AF:

0.00164

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0765

AC:

396

AN:

5174

South Asian (SAS)

AF:

0.00166

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0303

AC:

321

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68026

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00126

Hom.:

Bravo

AF:

0.00417

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

-0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.11

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