chr19-46746094-A-AGGCCG

Position:

• chr19-46746094-A-AGGCCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024301.5(FKRP):​c.-253+22_-253+26dup variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,242,240 control chromosomes in the GnomAD database, including 8,217 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (714 hom., cov: 28)
  • Exomes 𝑓: 0.12 (7503 hom.)
• Consequence: FKRP NM_024301.5 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0770

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-46746094-A-AGGCCG is Benign according to our data. Variant chr19-46746094-A-AGGCCG is described in ClinVar as [Benign]. Clinvar id is 516899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRN4	NM_013403.3	c.282+54_282+55insCGGCC		intron_variant		ENST00000263280.11	NP_037535.2
FKRP	NM_024301.5	c.-253+22_-253+26dup		splice_donor_region_variant, intron_variant		ENST00000318584.10	NP_077277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRN4	ENST00000263280.11	c.282+54_282+55insCGGCC		intron_variant		1	NM_013403.3	ENSP00000263280	P4
FKRP	ENST00000318584.10	c.-253+22_-253+26dup		splice_donor_region_variant, intron_variant		1	NM_024301.5	ENSP00000326570	P1

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 12920 AN: 145596 Hom.: 715 Cov.: 28

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.0441

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0826

Gnomad EAS AF: 0.00841

Gnomad SAS AF: 0.0518

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0791

GnomAD4 exome AF: 0.120 AC: 131185 AN: 1096538 Hom.: 7503 Cov.: 34 AF XY: 0.118 AC XY: 63325 AN XY: 535702

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.0650

Gnomad4 ASJ exome AF: 0.0975

Gnomad4 EAS exome AF: 0.00553

Gnomad4 SAS exome AF: 0.0466

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0887 AC: 12922 AN: 145702 Hom.: 714 Cov.: 28 AF XY: 0.0849 AC XY: 6030 AN XY: 71016

Gnomad4 AFR AF: 0.0506

Gnomad4 AMR AF: 0.0689

Gnomad4 ASJ AF: 0.0826

Gnomad4 EAS AF: 0.00844

Gnomad4 SAS AF: 0.0517

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.0779

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 07, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs568014119; hg19: chr19-47249351;