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GeneBe

12-69880291-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_182530.3(MYRFL):c.555G>A(p.Pro185=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 702,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 0 hom. )

Consequence

MYRFL
NM_182530.3 splice_region, synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.425
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-69880291-G-A is Benign according to our data. Variant chr12-69880291-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643172.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.425 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYRFLNM_182530.3 linkuse as main transcriptc.555G>A p.Pro185= splice_region_variant, synonymous_variant 5/25 ENST00000552032.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYRFLENST00000552032.7 linkuse as main transcriptc.555G>A p.Pro185= splice_region_variant, synonymous_variant 5/255 NM_182530.3 P2
MYRFLENST00000547771.6 linkuse as main transcriptc.555G>A p.Pro185= splice_region_variant, synonymous_variant 5/255 A2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00196
AC:
299
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000603
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00688
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00287
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00141
AC:
189
AN:
133624
Hom.:
0
AF XY:
0.00132
AC XY:
96
AN XY:
72730
show subpopulations
Gnomad AFR exome
AF:
0.000466
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.000121
Gnomad EAS exome
AF:
0.0000954
Gnomad SAS exome
AF:
0.0000447
Gnomad FIN exome
AF:
0.00744
Gnomad NFE exome
AF:
0.00248
Gnomad OTH exome
AF:
0.00146
GnomAD4 exome
AF:
0.00194
AC:
1070
AN:
550198
Hom.:
0
Cov.:
0
AF XY:
0.00176
AC XY:
524
AN XY:
297860
show subpopulations
Gnomad4 AFR exome
AF:
0.000506
Gnomad4 AMR exome
AF:
0.000260
Gnomad4 ASJ exome
AF:
0.0000499
Gnomad4 EAS exome
AF:
0.000374
Gnomad4 SAS exome
AF:
0.000112
Gnomad4 FIN exome
AF:
0.00494
Gnomad4 NFE exome
AF:
0.00259
Gnomad4 OTH exome
AF:
0.00157
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00196
AC:
299
AN:
152336
Hom.:
0
Cov.:
32
AF XY:
0.00201
AC XY:
150
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000601
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00688
Gnomad4 NFE
AF:
0.00287
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00158
Hom.:
0
Bravo
AF:
0.00153
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2022MYRFL: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
11
Dann
Benign
0.77

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138901473; hg19: chr12-70274071; API