dbSNP rs6843340: FRYL:c.411+1354G>A (chr4-48617920-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015030.2(FRYL):c.411+1354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,036 control chromosomes in the GnomAD database, including 22,179 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 0.53 ( 22175 hom., cov: 31)

Exomes 𝑓: 0.57 ( 4 hom. )

Consequence

FRYL
NM_015030.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

Publications

4 publications found

Variant links:

Genes affected

FRYL (HGNC:29127): (FRY like transcription coactivator) Predicted to be involved in cell morphogenesis and neuron projection development. Predicted to be active in cell cortex and site of polarized growth. [provided by Alliance of Genome Resources, Apr 2022]

FRYL Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
Pan-Chung-Bellen syndrome
Inheritance: AD Classification: MODERATE Submitted by: G2P

FRYL 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 (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015030.2. 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
	FRYL	NM_015030.2	MANE Select	c.411+1354G>A		intron	N/A	NP_055845.1	O94915-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FRYL	ENST00000358350.9	TSL:5 MANE Select	c.411+1354G>A	intron	N/A	ENSP00000351113.4	O94915-1
FRYL	ENST00000507873.8	TSL:1	c.411+1354G>A	intron	N/A	ENSP00000422408.4	A0A2C9F2R7
FRYL	ENST00000926452.1		c.411+1354G>A	intron	N/A	ENSP00000596511.1

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80623

AN:

151890

Hom.:

22155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.507

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.488

GnomAD4 exome

AF:

0.571

AC:

AN:

Hom.:

Cov.:

AF XY:

0.591

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

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:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.636

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.531

AC:

80684

AN:

152008

Hom.:

22175

Cov.:

AF XY:

0.528

AC XY:

39224

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.681

AC:

28232

AN:

41458

American (AMR)

AF:

0.382

AC:

5839

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

1761

AN:

3472

East Asian (EAS)

AF:

0.480

AC:

2484

AN:

5178

South Asian (SAS)

AF:

0.606

AC:

2918

AN:

4812

European-Finnish (FIN)

AF:

0.475

AC:

5009

AN:

10546

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.482

AC:

32761

AN:

67944

Other (OTH)

AF:

0.486

AC:

1027

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1910

3819

5729

7638

9548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<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:

0.570

Hom.:

6737

Bravo

AF:

0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.44

PhyloP100

-0.31

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over