rs789560

Positions:

• chr12-69938047-G-T

Variant summary

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

The NM_182530.3(MYRFL):​c.2224+1415G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 152,226 control chromosomes in the GnomAD database, including 765 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 0.089 (765 hom., cov: 33)
• Consequence: MYRFL NM_182530.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963

Genes affected

MYRFL (HGNC:26316): (myelin regulatory factor like) Predicted to enable DNA-binding transcription factor activity and sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated and protein autoprocessing. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

PRANCR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRFL	NM_182530.3	c.2224+1415G>T		intron_variant		ENST00000552032.7	NP_872336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRFL	ENST00000552032.7	c.2224+1415G>T		intron_variant		5	NM_182530.3	ENSP00000448753.2

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13563 AN: 152108 Hom.: 765 Cov.: 33

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0991

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

GnomAD4 genome AF: 0.0891 AC: 13564 AN: 152226 Hom.: 765 Cov.: 33 AF XY: 0.0881 AC XY: 6557 AN XY: 74416

Gnomad4 AFR AF: 0.0246

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.100

Alfa AF: 0.115 Hom.: 2328

Bravo AF: 0.0822

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs789560; hg19: chr12-70331827;