rs11668878

chr19-46765116-G-T

Variant summary

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

The ENST00000600646.5(FKRP):n.248-11536G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,186 control chromosomes in the GnomAD database, including 270 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 0.051 (270 hom., cov: 31)
• Consequence: FKRP ENST00000600646.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKRP	ENST00000600646.5	n.248-11536G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7682 AN: 152070 Hom.: 270 Cov.: 31

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0677

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

GnomAD4 genome AF: 0.0505 AC: 7688 AN: 152186 Hom.: 270 Cov.: 31 AF XY: 0.0501 AC XY: 3730 AN XY: 74408

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.0760

Gnomad4 OTH AF: 0.0670

Alfa AF: 0.0724 Hom.: 719

Bravo AF: 0.0492

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11668878; hg19: chr19-47268373;