chr17-4948472-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005022.4(PFN1):c.-78C>T variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00302 in 1,450,210 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 46 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 31 hom. )

Consequence

PFN1
NM_005022.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.74

Publications

2 publications found

Variant links:

Genes affected

PFN1 (HGNC:8881): (profilin 1) This gene encodes a member of the profilin family of small actin-binding proteins. The encoded protein plays an important role in actin dynamics by regulating actin polymerization in response to extracellular signals. Deletion of this gene is associated with Miller-Dieker syndrome, and the encoded protein may also play a role in Huntington disease. Multiple pseudogenes of this gene are located on chromosome 1. [provided by RefSeq, Jul 2012]

PFN1 links:

ENO3 (HGNC:3354): (enolase 3) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme is found in skeletal muscle cells in the adult where it may play a role in muscle development and regeneration. A switch from alpha enolase to beta enolase occurs in muscle tissue during development in rodents. Mutations in this gene have be associated glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jul 2010]

ENO3 Gene-Disease associations (from GenCC):

glycogen storage disease due to muscle beta-enolase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ENO3 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 (MetaRNN=0.0027508438).

BP6

Variant 17-4948472-G-A is Benign according to our data. Variant chr17-4948472-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0152 (2313/152230) while in subpopulation AFR AF = 0.0509 (2116/41536). AF 95% confidence interval is 0.0491. There are 46 homozygotes in GnomAd4. There are 1093 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2313 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005022.4. 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
	PFN1	NM_005022.4	MANE Select	c.-78C>T		5_prime_UTR	Exon 1 of 3	NP_005013.1	P07737
	PFN1	NM_001375991.1		c.-78C>T		5_prime_UTR	Exon 1 of 2	NP_001362920.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PFN1	ENST00000225655.6	TSL:1 MANE Select	c.-78C>T		5_prime_UTR	Exon 1 of 3	ENSP00000225655.5	P07737
PFN1	ENST00000572383.1	TSL:3	c.160C>T	p.Pro54Ser	missense	Exon 2 of 3	ENSP00000460363.1	I3L3D5
PFN1	ENST00000929513.1		c.-78C>T		5_prime_UTR	Exon 1 of 3	ENSP00000599572.1

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2312

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0510

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00825

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00479

AC:

381

AN:

79522

AF XY:

0.00344

show subpopulations

Gnomad AFR exome

AF:

0.0649

Gnomad AMR exome

AF:

0.00649

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000435

Gnomad OTH exome

AF:

0.00260

GnomAD4 exome

AF:

0.00159

AC:

2069

AN:

1297980

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

861

AN XY:

635786

show subpopulations

African (AFR)

AF:

0.0517

AC:

1374

AN:

26600

American (AMR)

AF:

0.00588

AC:

134

AN:

22808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19566

East Asian (EAS)

AF:

0.00

AC:

AN:

31626

South Asian (SAS)

AF:

0.000312

AC:

AN:

67288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33460

Middle Eastern (MID)

AF:

0.00250

AC:

AN:

5210

European-Non Finnish (NFE)

AF:

0.000312

AC:

324

AN:

1037670

Other (OTH)

AF:

0.00378

AC:

203

AN:

53752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

107

215

322

430

537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0152

AC:

2313

AN:

152230

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1093

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0509

AC:

2116

AN:

41536

American (AMR)

AF:

0.00824

AC:

126

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

67994

Other (OTH)

AF:

0.0147

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

110

221

331

442

552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.000744

Hom.:

Bravo

AF:

0.0173

ExAC

AF:

0.00410

AC:

458

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

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0078

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0028

PhyloP100

3.7

MVP

0.74

GERP RS

3.1

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Mutation Taster

=294/6

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over