GeneBe

19-46746104-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013403.3(STRN4):​c.282+45C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000787 in 1,271,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

STRN4
NM_013403.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.798

Publications

0 publications found
Variant links:
Genes affected
STRN4 (HGNC:15721): (striatin 4) Enables armadillo repeat domain binding activity and protein phosphatase 2A binding activity. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]
FKRP (HGNC:17997): (fukutin related protein) This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]
FKRP Gene-Disease associations (from GenCC):
  • autosomal recessive limb-girdle muscular dystrophy type 2I
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Ambry Genetics
  • muscular dystrophy-dystroglycanopathy type B5
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
  • myopathy caused by variation in FKRP
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • congenital muscular dystrophy with cerebellar involvement
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • congenital muscular dystrophy with intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • congenital muscular dystrophy without intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • muscle-eye-brain disease
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • muscular dystrophy-dystroglycanopathy, type A
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STRN4NM_013403.3 linkc.282+45C>A intron_variant Intron 1 of 17 ENST00000263280.11 NP_037535.2 Q9NRL3-1
FKRPNM_024301.5 linkc.-253+14G>T intron_variant Intron 1 of 3 ENST00000318584.10 NP_077277.1 Q9H9S5A0A024R0R7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STRN4ENST00000263280.11 linkc.282+45C>A intron_variant Intron 1 of 17 1 NM_013403.3 ENSP00000263280.4 Q9NRL3-1
FKRPENST00000318584.10 linkc.-253+14G>T intron_variant Intron 1 of 3 1 NM_024301.5 ENSP00000326570.4 Q9H9S5

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
7.87e-7
AC:
1
AN:
1271004
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
626654
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
25108
American (AMR)
AF:
0.00
AC:
0
AN:
20554
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20406
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26522
South Asian (SAS)
AF:
0.00
AC:
0
AN:
68390
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33428
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4574
European-Non Finnish (NFE)
AF:
9.80e-7
AC:
1
AN:
1020608
Other (OTH)
AF:
0.00
AC:
0
AN:
51414
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
11
DANN
Benign
0.84
PhyloP100
0.80
PromoterAI
0.18
Neutral
RBP_binding_hub_radar
0.67
RBP_regulation_power_radar
3.3

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

Other links and lift over

dbSNP: rs755990039; hg19: chr19-47249361; API