rs11673198

Positions:

• chr19-46774455-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000600646.5(FKRP):​n.248-2197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,572 control chromosomes in the GnomAD database, including 3,812 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 0.22 (3812 hom., cov: 28)
• Consequence: FKRP ENST00000600646.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

Genes affected

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000600646.5	n.248-2197C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32848 AN: 151452 Hom.: 3807 Cov.: 28

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 32876 AN: 151572 Hom.: 3812 Cov.: 28 AF XY: 0.222 AC XY: 16421 AN XY: 74040

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.216

Alfa AF: 0.191 Hom.: 385

Bravo AF: 0.229

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11673198; hg19: chr19-47277712;