rs2054591393

Variant names:

• chr19-46746073-C-G
• rs2054591393
• NM_024301.5:c.-270C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-46746073-C-G
• chr19-46746073-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024301.5(FKRP):​c.-270C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 999,216 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: FKRP NM_024301.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKRP	NM_024301.5	c.-270C>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000318584.10	NP_077277.1
STRN4	NM_013403.3	c.282+76G>C		intron_variant	Intron 1 of 17	ENST00000263280.11	NP_037535.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000318584.10	c.-270C>G		5_prime_UTR_variant	Exon 1 of 4	1	NM_024301.5	ENSP00000326570.4
STRN4	ENST00000263280.11	c.282+76G>C		intron_variant	Intron 1 of 17	1	NM_013403.3	ENSP00000263280.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000200 AC: 2 AN: 999216 Hom.: 0 Cov.: 27 AF XY: 0.00000411 AC XY: 2 AN XY: 486794

African (AFR) AF: 0.00 AC: 0 AN: 17600

American (AMR) AF: 0.00 AC: 0 AN: 6144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11030

East Asian (EAS) AF: 0.00 AC: 0 AN: 20204

South Asian (SAS) AF: 0.00 AC: 0 AN: 42504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2744

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 840500

Other (OTH) AF: 0.00 AC: 0 AN: 38360

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Benign	0.93
PhyloP100		-0.17
PromoterAI		-0.87	Under-expression
Mutation Taster		=264/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2054591393; hg19: chr19-47249330;