Genetic Variant NM_182530.3:c.555G>A (chr12-69880291-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_182530.3(MYRFL):c.555G>A(p.Pro185Pro) 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

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.425

Publications

0 publications found

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]

MYRFL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 12-69880291-G-A is Benign according to our data. Variant chr12-69880291-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2643172.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.425 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182530.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRFL	NM_182530.3	MANE Select	c.555G>A	p.Pro185Pro	splice_region synonymous	Exon 5 of 25	NP_872336.2	Q96LU7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYRFL	ENST00000552032.7	TSL:5 MANE Select	c.555G>A	p.Pro185Pro	splice_region synonymous	Exon 5 of 25	ENSP00000448753.2	Q96LU7
MYRFL	ENST00000535034.6	TSL:1	c.555G>A	p.Pro185Pro	splice_region synonymous	Exon 5 of 24	ENSP00000440626.2
MYRFL	ENST00000547771.6	TSL:5	c.555G>A	p.Pro185Pro	splice_region synonymous	Exon 5 of 25	ENSP00000449598.2	F8VVR8

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

299

AN:

152218

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00141

AC:

189

AN:

133624

AF XY:

0.00132

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 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.:

Cov.:

AF XY:

0.00176

AC XY:

524

AN XY:

297860

show subpopulations

African (AFR)

AF:

0.000506

AC:

AN:

15796

American (AMR)

AF:

0.000260

AC:

AN:

34676

Ashkenazi Jewish (ASJ)

AF:

0.0000499

AC:

AN:

20022

East Asian (EAS)

AF:

0.000374

AC:

AN:

32094

South Asian (SAS)

AF:

0.000112

AC:

AN:

62676

European-Finnish (FIN)

AF:

0.00494

AC:

166

AN:

33612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4070

European-Non Finnish (NFE)

AF:

0.00259

AC:

819

AN:

316676

Other (OTH)

AF:

0.00157

AC:

AN:

30576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00196

AC:

299

AN:

152336

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41576

American (AMR)

AF:

0.000261

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00688

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00287

AC:

195

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.00153

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.42

Mutation Taster

=72/28

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over