rs11670473

Positions:

• chr19-46754224-G-A

Variant summary

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

The NM_024301.5(FKRP):​c.-39-1188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,906 control chromosomes in the GnomAD database, including 2,870 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 0.18 (2870 hom., cov: 30)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: FKRP NM_024301.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKRP	NM_024301.5	c.-39-1188G>A		intron_variant		ENST00000318584.10	NP_077277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000318584.10	c.-39-1188G>A		intron_variant		1	NM_024301.5	ENSP00000326570	P1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27087 AN: 151762 Hom.: 2867 Cov.: 30

Gnomad AFR AF: 0.0900

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.206

GnomAD4 exome AF: 0.167 AC: 4 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.222 AC XY: 4 AN XY: 18

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.182

GnomAD4 genome AF: 0.178 AC: 27094 AN: 151882 Hom.: 2870 Cov.: 30 AF XY: 0.176 AC XY: 13099 AN XY: 74222

Gnomad4 AFR AF: 0.0898

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.203

Alfa AF: 0.234 Hom.: 5157

Bravo AF: 0.169

Asia WGS AF: 0.0680 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11670473; hg19: chr19-47257481;