12-69938047-G-T

Variant names:

• chr12-69938047-G-T
• rs789560
• NM_182530.3:c.2224+1415G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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:51126): (progenitor renewal associated non-coding RNA)

ACMG classification

Our verdict: Benign. The variant received -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.

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.2224+1415G>T		intron	N/A	NP_872336.2	Q96LU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRFL	ENST00000552032.7	TSL:5 MANE Select	c.2224+1415G>T		intron	N/A	ENSP00000448753.2	Q96LU7
	MYRFL	ENST00000535034.6	TSL:1	c.2224+1415G>T		intron	N/A	ENSP00000440626.2
	MYRFL	ENST00000547771.6	TSL:5	c.2191+1415G>T		intron	N/A	ENSP00000449598.2	F8VVR8

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

African (AFR) AF: 0.0246 AC: 1022 AN: 41546

American (AMR) AF: 0.0679 AC: 1038 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 424 AN: 3472

East Asian (EAS) AF: 0.110 AC: 570 AN: 5182

South Asian (SAS) AF: 0.0549 AC: 265 AN: 4828

European-Finnish (FIN) AF: 0.130 AC: 1377 AN: 10588

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8467 AN: 67998

Other (OTH) AF: 0.100 AC: 211 AN: 2110

Alfa AF: 0.110 Hom.: 4123

Bravo AF: 0.0822

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.54
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs789560; hg19: chr12-70331827;