19-46746094-AGGCCGGGCCG-AGGCCG

Variant names:

• chr19-46746094-AGGCCG-A
• rs568014119
• NM_013403.3:c.282+50_282+54delCGGCC

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The ENST00000318584.10(FKRP):​c.-253+5_-253+9delGGCCG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 1,244,078 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00032 (1 hom.)
• Consequence: FKRP ENST00000318584.10 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-46746094-AGGCCG-A is Benign according to our data. Variant chr19-46746094-AGGCCG-A is described in Lovd as [Likely_benign]. Variant chr19-46746094-AGGCCG-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00248 (361/145788) while in subpopulation AFR AF= 0.00833 (329/39484). AF 95% confidence interval is 0.00759. There are 0 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRN4	NM_013403.3	c.282+50_282+54delCGGCC		intron_variant	Intron 1 of 17	ENST00000263280.11	NP_037535.2
FKRP	NM_024301.5	c.-253+22_-253+26delCCGGG		intron_variant	Intron 1 of 3	ENST00000318584.10	NP_077277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRN4	ENST00000263280.11	c.282+50_282+54delCGGCC		intron_variant	Intron 1 of 17	1	NM_013403.3	ENSP00000263280.4
FKRP	ENST00000318584.10	c.-253+5_-253+9delGGCCG		splice_region_variant, intron_variant	Intron 1 of 3	1	NM_024301.5	ENSP00000326570.4

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 359 AN: 145682 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00830

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000647

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.00200

GnomAD4 exome AF: 0.000316 AC: 347 AN: 1098290 Hom.: 1 AF XY: 0.000283 AC XY: 152 AN XY: 536622

Gnomad4 AFR exome AF: 0.00980

Gnomad4 AMR exome AF: 0.000755

Gnomad4 ASJ exome AF: 0.0000775

Gnomad4 EAS exome AF: 0.000182

Gnomad4 SAS exome AF: 0.000284

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000112

Gnomad4 OTH exome AF: 0.000537

GnomAD4 genome AF: 0.00248 AC: 361 AN: 145788 Hom.: 0 Cov.: 28 AF XY: 0.00221 AC XY: 157 AN XY: 71050

Gnomad4 AFR AF: 0.00833

Gnomad4 AMR AF: 0.00101

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000649

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.00198

ClinVar

Not reported in ClinVar

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;